The U.S. and Israel launched a major attack on targets across Iran on Saturday, and U.S. President Donald Trump called on the Iranian people to “take over your government” — an extraordinary appeal that suggested the allies could be seeking to end of the country’s theocracy after decades of tensions.

The first strikes of the attack appeared to target the compound home to Iran’s 86-year-old Supreme Leader Ayatollah Ali Khamenei in downtown Tehran. It wasn’t immediately clear if he was there at the time. Smoke could be seen rising from the Iranian capital.

“For 47 years, the Iranian regime has chanted Death to America and waged an unending campaign of bloodshed and mass murder, targeting the United States, our troops and the innocent people in many, many countries,” Trump said in a video posted on social media that sought to justify the attacks. He urged Iranians to take cover during the strikes, but then: “When we are finished, take over your government. It will be yours to take.”

The attack quickly expanded beyond Iran. Iran’s paramilitary Revolutionary Guard said it responded by launching a “first wave” of drones and missiles targeting Israel, where a nationwide warning was issued as the military said it bring down Iranian fire.

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.

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.”

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

On Saturday, Trump said in the video that the U.S. had begun “major combat operations in Iran.” Trump claimed that Iran has continued to develop its nuclear program and plans to develop missiles to reach U.S. He acknowledged that there could be American casualties following Iran strikes, saying “that often happens in war.”

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But 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.

Prime Minister Benjamin Netanyahu of Israel — which considers Iran its archenemy — said the joint attack was to “remove an existential threat posed” by Iran.

“Our joint operation will create the conditions for the brave Iranian people to take their fate into their own hands,” Netanyahu said.

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 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.

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.

Hours after the strikes, Iran’s paramilitary Revolutionary Guard said it launched a “first wave” of drones and missiles targeting Israel. It had vowed to respond if attacked, including saying American military personnel and bases spread across the region would be targets.

Explosions rocked Israel as the country worked to intercept incoming Iranian missiles. There was no immediate word on any damage or casualties from the ongoing attack.

Several hospitals in Israel launched their emergency protocols, including moving patients and surgeries to underground facilities.

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.”

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.

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.

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Toropin reported from Washington and Boak from West Palm Beach, Florida. Associated Press writers Melanie Lidman and Sam Mednick in Tel Aviv, Israel, contributed to this report.

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