US President Donald Trump says Iran's Supreme Leader Ayatollah Ali Khamenei has been killed in air strikes by the United States and Israel.
On Truth Social, President Trump wrote: "Khamenei, one of the most evil people in History, is dead."
"This is not only Justice for the people of Iran, but for all Great Americans, and those people from many Countries throughout the World, that have been killed or mutilated by Khamenei and his gang of bloodthirsty THUGS," he wrote.
Earlier, multiple sources cited an unnamed Israeli official as saying Khamenei had been killed and his body had been found.
Iranian state media also confirmed Khamenei was dead, after earlier claims by the regime that he was "safe and sound".
Khamenei's daughter, grandchild, daughter-in-law and son-in-law were also killed in the strikes.
UN Secretary-General UN Secretary-General António Guterres could not confirm Khamenei's death, saying the situation on the ground in Iran was "very fluid".
In a televised address, Israeli Prime Minister Benjamin Netanyahu said there were signs Iran's leader "is no longer" after the strike, but could not confirm his death.
"There are many signs that this tyrant is no longer," he said. "This morning we eliminated senior officials in the ayatollah's regime, Revolutionary Guards commanders, senior figures in the nuclear program — and we will continue."
Iran has retaliated by launching missiles and drones across the Middle East, after the US and Israel launched strikes aimed at forcing regime change in the Islamic republic.
Mr Trump called on Iranians to "rise up" against their rulers as he confirmed on Saturday, in the biggest foreign policy gamble of his presidency, that America and Israel had begun joint and "ongoing" military action against Iran.
Tehran called the strikes, which began in the morning hours and hit targets in different areas of the country, unprovoked and illegal.
In the first wave of strikes, the compound of Iranian Supreme Leader Ayatollah Ali Khamenei was targeted.
In cities across Iran, explosions caused widespread panic. Residents rushed to collect children from school and flee areas that might be targeted.
Iran responded by launching missiles at Israel and several Gulf Arab allies of the United States that host American bases.
Iran issued a warning to shipping that the Strait of Hormuz, the narrow passage through which about a fifth of global oil passes, had been closed. Traders expected a sharp jump in oil prices. Airlines cancelled flights in the Middle East.
Tehran promised a stronger response to come, with a senior Iranian Revolutionary Guards commander, Ebrahim Jabbari, saying it had so far used only "scrap missiles" and would soon unveil unforeseen weapons.
Mr Guterres spoke at an emergency Security Council meeting in New York on Saturday morning, local time, and urged immediate de-escalation in the region.
"Since this morning, I have condemned the massive military strikes by the United States and Israel against Iran," he said.
"And I also condemn the subsequent attacks by Iran, violating the sovereignty and territorial integrity of Iraq, Qatar, Saudi Arabia and the United Arab Emirates."
Israel's military said its pilots had hit hundreds of targets throughout Iran including strategic defence systems already damaged in strikes last year. It said three sites where leaders had been meeting were struck simultaneously and several senior figures were killed.
Iranian Defence Minister Amir Nasirzadeh and Revolutionary Guard commander Mohammed Pakpour were killed in the Israeli attacks, three sources familiar with the matter said.
Australia's Foreign Minister Penny Wong said Australia did not participate in the operation and was not warned in advance.
The first wave of strikes in what the Pentagon named Operation Epic Fury mainly targeted Iranian officials, a source said.
An Iranian source close to the establishment said several senior commanders in Iran's Revolutionary Guards and political officials had been killed.
The Iranian ambassador to the United Nations said a girls' primary school in the southern town of Minab was hit, leaving more than 100 children dead.
"The number of innocent civilians continues to rise. This is not only an act of aggression, it is a war crime and a crime against humanity," Amir Saeid Iravani told an emergency meeting of the UN Security Council.
Trump says 'bombs will be dropping everywhere'
In a video message published on social media, Mr Trump cited Washington's decades-old dispute with Iran and attacks dating to the seizure of the US embassy in Tehran during the 1979 Islamic revolution that brought the clerics to power.
The president said the aim was "eliminating imminent threats from the Iranian regime" and urged Iranians to stay sheltered because "bombs will be dropping everywhere".
"When we are finished, take over your government. It will be yours to take. This will be probably your only chance for generations," he added.
Mr Netanyahu said the joint US-Israeli attack "will create the conditions for the brave Iranian people to take their destiny into their own hands" and "remove the yoke of tyranny".
Iran's clerical leaders were already in a difficult position after mass anti-government demonstrations in January, which led to a crackdown in which thousands of people were killed in the worst domestic unrest since the era of the 1979 revolution.
Protesters had again taken to the streets in recent days in remembrance of those killed the previous month.
Israeli military operations over the past two years killed some of Iran's senior military officials and severely weakened several of Tehran's once-feared proxy forces across the Middle East.
After Israel pounded Iran in a 12-day air war in June, joined by the United States, the US and Israel warned they would strike again if Iran pressed ahead with its nuclear and ballistic missile programs.
The threats were backed up in recent weeks by a US military build-up in the region, even as Iranian and US officials held nuclear talks.
Missiles fired at Gulf states
Oil markets have been closely watching the stand-off between Washington and Tehran to try and determine if supplies will be impacted.
Jorge Leon, head of geopolitical analysis at Rystad Energy, predicted prices could shoot up by $US10-20 per barrel when markets opened on Monday unless there were signs of de-escalation.
Iran, the third-largest producer in the Organization of Petroleum Exporting Countries (OPEC), pumps about 4 per cent of global oil supplies, and a far larger share is shipped past its coast through the strait leading out of the Gulf.
Iran's Revolutionary Guard said all US bases and interests in the region were within Iran's reach and that Iran's retaliation would continue until "the enemy is decisively defeated".
In Israel, sirens and mobile phone warnings sent Israelis rushing to air raid shelters as Iran launched a series of missile barrages. At least one woman died, according to Israel's rescue services.
At least two people were killed by Iranian strikes targeting the Jurf al-Nasr area in Iraq's Babil province, according to the Iraqi army.
Loud booms sounded in Abu Dhabi, the capital of the United Arab Emirates, an oil producer and close US ally, and several blasts were heard in the business capital Dubai, where one of the city's plush hotel districts was also hit.
Abu Dhabi Airports said one person was killed in an incident at Zayed International Airport.
In a separate incident, the UAE foreign ministry said one Pakistani national was killed, reportedly by falling debris from a missile strike.
Bahrain said the service centre of the US Fifth Fleet — the base for American naval forces in the region — had been subjected to a missile attack. Video footage showed a thick grey plume of smoke rising from near the island state's coastline.
Qatar said it had downed all missiles targeting the country and that it had a right to respond. Kuwait confirmed a missile attack on a US military base there.