DUBAI, United Arab Emirates (AP) — The U.S. and Israel launched a major attack on Iran on Saturday, with President Donald Trump calling on the Iranian public to “seize control of your destiny” and rise 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, and 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.

They came after tensions soared in recent weeks as American warships moved into the region, and 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.

Iran responded 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 that 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.”

Five students were reported killed at girls’ school in southern Iran in the Israeli-U.S. strikes, according to Iran’s state-run IRNA news agency. 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

Israel said the operation was carried out as a “broad, coordinated, and joint operation against the regime” that 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.

“They’ve rejected every opportunity to renounce their nuclear ambitions, and we can’t take it anymore,” Trump said.

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. There is no public evidence of Iran seeking to have intercontinental ballistic missiles, though Washington has criticized its space program as potentially allowing it to one day.

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 also have a huge impact on 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.

In Tehran, witnesses heard the first blast by Khamenei’s office. Iranian state television later reported on the explosion, without offering a cause.

More explosions struck Iran’s capital after Israel said it was attacking the country. Authorities have offered no casualty information from the strikes.

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.

Iraq and the United Arab Emirates closed their airspace, and sirens sounded in Jordan.

The Iranian-backed Houthis in Yemen, meanwhile, 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.”