Iran said the Strait of Hormuz, crucial to oil and other exports, would be "completely closed" immediately if the US follows up on US President Donald Trump's threat to attack its power plants.
Trump set a 48-hour deadline late on Saturday to open the strait.
Israeli leaders visited one of two southern communities near a secretive nuclear research site struck by Iranian missiles late on Saturday, with scores of people wounded.
Prime Minister Benjamin Netanyahu said it was a "miracle" no-one was killed. Israel detected more Iranian missiles fired towards the area.
"If anyone needed an explanation of why Iran is the enemy of civilization, and the enemy and the danger to the entire world. You got it in the last 48 hours," he said.
Netanyahu claimed Israel and the US were well on their way to achieving their war goals.
The aims have ranged from weakening Iran's nuclear program, missile program and support for armed proxies to enabling the Iranian people to overthrow the theocracy.
The developments signalled the war, which the US and Israel launched on February 28, was moving in a dangerous new direction, despite Trump's comment last week that he was considering "winding down" operations.
It has killed more than 2000 people, rattled the global economy and sent oil prices surging.
The Iranian-backed Hezbollah claimed responsibility for an airstrike that killed a man in northern Israel, while Lebanese President Joseph Aoun called Israel's targeting of bridges in the south "a prelude to a ground invasion".
Iran has practically closed the Strait of Hormuz that connects the Persian Gulf to the rest of the world, while claiming safe passage for vessels from countries other than its enemies.
Roughly one-fifth of global oil supply passes through the strait, but attacks on ships have stopped nearly all tanker traffic.
Trump said if Iran did not open the strait, the US would destroy its "various POWER PLANTS, STARTING WITH THE BIGGEST ONE FIRST!"
The US has argued that Iran's Revolutionary Guard controls much of the country's infrastructure and uses it to power the war effort.
Under international law, power plants that benefit civilians can be targeted only if the military advantage outweighs the suffering it causes them, legal scholars say.
Iranian parliament speaker Mohammad Bagher Qalibaf responded on X that if Iran's power plants and infrastructure are targeted, then vital infrastructure across the region - including energy and desalination facilities critical for drinking water in Gulf nations - would be considered legitimate targets and "irreversibly destroyed".
Qalibaf later added that "entities that finance the US military budget are legitimate targets".
Attacks on power plants would be "inherently indiscriminate and clearly disproportionate", Iran's UN ambassador wrote to the security council, according to the state-run IRNA news agency.
Iran said its strikes in the Negev Desert late on Saturday were in retaliation for an earlier attack on Iran's main nuclear enrichment site in Natanz, according to state-run media.
Tehran praised the attack as a show of strength, even as Israel's military asserts that Iranian missile launches have gradually decreased in frequency since the war began.
Southern Israel's main hospital received at least 175 wounded from Arad and Dimona, its deputy director Roy Kessous told The Associated Press.
Israel is widely believed to possess nuclear weapons, although it does not confirm or deny their existence.
Israel denied responsibility for hitting Natanz on Saturday, while the Iranian judiciary's official news agency, Mizan, said there was no leakage. The Pentagon declined to comment on the strike.
The International Atomic Energy Agency has said the bulk of Iran's estimated 440kg of enriched uranium - the issue at the heart of tensions - is elsewhere, beneath the rubble at its Isfahan facility.
Director General Rafael Grossi said stressed that "maximum military restraint should be observed, in particular in the vicinity of nuclear facilities".
Iran said strikes hit a hospital in Andimeshk. Its health ministry said patients and doctors were evacuated to another city.
Iran's death toll in the war has surpassed 1500, state media reported on Saturday, citing the
Lebanese authorities say Israel's strikes have killed more than 1000 people and displaced more than one million.
Meanwhile, Hezbollah has fired hundreds of rockets into Israel.
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