DUBAI, United Arab Emirates (AP) — The U.S. and Israel launched a major attack on Iran on Saturday, and President Donald Trump called on the Iranian public to “seize control of your destiny” by rising up against the Islamic leadership that has ruled the nation since 1979.

Some of the first strikes appeared to hit areas around the offices of Supreme Leader Ayatollah Ali Khamenei, and Iranian media reported strikes nationwide. Smoke could be seen rising from the capital. It wasn’t immediately clear whether the 86-year-old leader was in his offices at the time of the strike.

“When we are finished, take over your government. It will be yours to take. This will be probably your only chance for generations,” Trump said in a video announcing “major combat operations” were underway. “For many years, you have asked for America’s help, but you never got it.”

Israeli Prime Minister Benjamin Netanyahu echoed that sweeping goal. “Our joint operation will create the conditions for the brave Iranian people to take their fate into their own hands,” Netanyahu said.

The strikes opened a stunning new chapter in U.S. intervention in Iran and marked the second time in eight months that the Trump administration has used military force against the Islamic Republic. They also came just weeks after Trump ordered a military operation to capture Venezuela’s president, Nicolás Maduro, and bring him and his wife to New York to face federal drug conspiracy charges.

The targets included members of Iran's leadership, according to a U.S. official and another person briefed on the attacks who both spoke on condition of anonymity because they were discussing classified information on an ongoing operation. There was no immediate information on whether top officials had been killed.

Tensions have soared in recent weeks as American warships moved into the region. Trump said he wanted a deal to constrain Iran’s nuclear program at a moment when the country is struggling at home with growing dissent following nationwide protests.

The immediate trigger for Saturday’s strikes appears to be the unsuccessful latest round of nuclear talks. But they also reflect the dramatic changes across the region that have left Iran’s leadership in its weakest position since the Islamic Revolution nearly half a century ago.

Israeli and American strikes last June greatly weakened Iran’s air defenses, military leadership and nuclear program. A regionwide war, sparked by Hamas’ Oct. 7, 2023, attack on Israel, has left Iran’s network of proxies across the Middle East greatly weakened. U.S. sanctions and global isolation, meanwhile, have decimated Iran’s economy.

Iran responded to the latest strikes as it had been threatening to do for months — first launching a wave of missiles and drones targeting Israel. It followed with strikes targeting U.S. military installations in Bahrain, Kuwait and Qatar. The United Arab Emirates and Iraq shut down their airspace.

Iran’s Foreign Ministry issued a defiant statement, saying the country “will not hesitate” in its response. In a statement posted on X, the ministry said: “The time has come to defend the homeland and confront the enemy’s military assault.”

At least 57 people were reported killed at a girls’ school in southern Iran in the Israeli-U.S. strikes, according to Iran’s state-run IRNA news agency. At least 45 others were wounded in the attack in Minab in Iran’s Hormozgan province. The White House and the Israeli military did not immediately respond to a request for comment on reported strike on the school.

In an indication of the scope of the conflict, flights across the Middle East were disrupted and air defense fire thudded over Dubai, the commercial capital of the United Arab Emirates, Saturday afternoon. Associated Press journalists saw the aftereffects of the blast from an interceptor.

Shrapnel from an Iranian missile attack on the capital of the UAE killed one person, state media said.

Attack was coordinated between Israel and US
The U.S. military has for weeks amassed forces in the region, even as U.S. and Iranian envoys held talks in Switzerland and Oman aimed at finding a diplomatic solution.

“Active and serious negotiations have yet again been undermined,” Oman’s Foreign Minister Badr al-Busaidi said in a post on X. Al-Busaidi, a key mediator in the nuclear talks, traveled to Washington on Friday to meet with Vice President JD Vance.

“Neither the interests of the United States nor the cause of global peace are well served by this," al-Busaidi said. "And I pray for the innocents who will suffer. I urge the United States not to get sucked in further.”

Israel said the operation has been planned for months between the Israeli and U.S. militaries.

Trump, in justifying the military action, claimed that Iran has continued to develop its nuclear program and plans to develop missiles to reach the U.S.

He also acknowledged that there could be American casualties, saying “that often happens in war.”

It was a notable call on Americans to brace themselves from a U.S. leader who swept into office on an “America First” platform and vowed to keep out of “forever wars” that had bogged down his recent predecessors.

Trump’s statement indicated the U.S. was striking for reasons far beyond the nuclear program, listing grievances stretching back to the beginning of the Islamic Republic following a revolution in 1979 that turned Iran from one of America’s closest allies in the Middle East into a fierce foe.

The U.S. president said he was aiming to “annihilate” the Iranian navy and destroy regional proxies supported by Tehran.

He also called on the Iranian Revolutionary Guard to lay down its arms, pledging that members would be given immunity, while warning they would face “certain death” if they didn’t.

Trump had threatened military action — but held off — following Iran's recent crackdown on protests spurred by economic grievances and evolved into a nationwide, anti-government push against the ruling clerics.

The Human Rights Activists News Agency says it confirmed more than 7,000 deaths in the crackdown and that it is investigating thousands more. The government has acknowledged more than 3,000 killed, though it has undercounted or not reported fatalities from past unrest.

Iran has said it hasn’t enriched since June, but it has blocked international inspectors from visiting the sites America bombed during a 12-day war then. Satellite photos analyzed by The Associated Press have shown new activity at two of those sites, suggesting Iran is trying to assess and potentially recover material there.

Iran currently has a self-imposed limit on its ballistic missile program, limiting their range to 2,000 kilometers (1,240 miles). That puts all the Mideast and some of Eastern Europe in their range.

Iran had hoped to avert a war, but maintains it has the right to enrich uranium and does not want to discuss other issues, like its long-range missile program or support for armed groups like Hamas and Hezbollah.

The strikes could rattle global markets, particularly if Iran is able to make the Strait of Hormuz unsafe for commercial traffic. More than 14 million barrels per day of oil passed through the strait in 2025, about a third of total worldwide oil exports transported by sea.

Strikes hit targets across Iran
Iranian media reported strikes nationwide. Roads to Khamenei's compound in downtown Tehran had been shut down by authorities as other blasts rang out across the capital.

Khamenei has not made a public appearance in recent days and wasn't immediately seen after. During the 12-day war in June, he was believed to have been taken to a secure location away from his Tehran compound.

Targets in the Israeli campaign included Iran’s military, symbols of government and intelligence targets, according to an official briefed on the operation, who spoke on condition of anonymity to discuss nonpublic information on the attack.

Iran retaliates
Hours after the strikes, Iran’s paramilitary Revolutionary Guard said it launched a “first wave” of drones and missiles targeting Israel, where a nationwide warning was issued as the military said it was working to intercept incoming Iranian missiles. There was no immediate word on any damage or casualties from the ongoing attack.

Meanwhile, Bahrain said that a missile attack targeted the U.S. Navy’s 5th Fleet headquarters in the island kingdom. Witnesses heard sirens and explosions in Kuwait, home to U.S. Army Central. Explosions could be also be heard in Qatar.

The Iranian-backed Houthis in Yemen vowed to resume attacks on Red Sea shipping routes and on Israel, according to two senior Houthi officials. They spoke on condition of anonymity because there was no official announcement from the Houthi leadership.

U.S. embassies or consulates in Qatar, United Arab Emirates and Israel posted on social media that they told staffers to shelter in place and recommended all Americans “do the same until further notice.”