Israeli warplanes carried out coordinated strikes against the Natanz uranium enrichment complex and the Parchin military-industrial site overnight into Saturday in what the Israel Defense Forces described as the largest single-night air campaign of the five-week war, while two further attacks on U.S. positions in Iraq pushed the cumulative American combat death toll toward 330.

The Israeli operation, which the IDF said involved more than 90 fighter aircraft, multiple aerial refueling tankers and a sustained suppression-of-enemy-air-defenses package, began shortly after 1 a.m. local time and continued in successive waves for nearly four hours. The strikes targeted what an IDF statement called “the production, weaponization and command spine” of Iran’s nuclear and missile programs, including aboveground centrifuge halls at Natanz, the Parchin high-explosives test range east of Tehran and a previously undisclosed warhead-integration facility near the city of Khojir.

The campaign was framed by Israeli officials as the long-promised answer to Thursday’s massive Iranian barrage on Israeli cities, which killed 14 civilians and exposed gaps in the country’s layered air defenses. Prime Minister Benjamin Netanyahu, in a recorded statement broadcast on national television shortly before 6 a.m., said Israel had acted “with precision, with patience, and without illusion.”

“We have set back the Iranian nuclear weapons project by years tonight,” Netanyahu said. “We have struck the factories that build the missiles that fall on our children. The cabinet authorized this operation unanimously, and the operation is not yet complete.”

Satellite imagery analysts at the Middlebury Institute and at Maxar, which began releasing initial post-strike assessments Saturday afternoon, said significant structural damage was visible at Natanz, including the partial collapse of two aboveground centrifuge assembly buildings and extensive cratering at the perimeter of the underground Fordow access tunnels. The Parchin site, ringed by secondary explosions, was still smoldering in imagery captured at midday. Karim Sadjadpour, a non-resident fellow at the Carnegie Endowment for International Peace, said the pattern of targeting suggested Israel had moved beyond deterrence into a sustained campaign to “physically dismantle” Iran’s threshold capability.

“The choice of Natanz aboveground halls, Parchin and Khojir tells you this is no longer about messaging,” Sadjadpour said in a telephone interview. “Israel is trying to push the program back to a point where, even after a ceasefire, reconstitution would take years rather than months.”

Iranian state television confirmed strikes at Natanz, Parchin and “several other locations” but disputed the scale of the damage, broadcasting footage of intact gates at Natanz and interviewing workers who said the underground halls had been emptied weeks ago. The Atomic Energy Organization of Iran said in a brief statement that “no radioactive release” had been detected and that all enrichment work would continue. Foreign Minister Abbas Araghchi, speaking to reporters in Tehran, called the strikes “a war crime that will not go unanswered” and said Iran reserved “every legitimate right” of retaliation.

Inside Iran, the human toll was beginning to come into focus. The semi-official Tasnim news agency reported at least 47 deaths and more than 200 wounded across the targeted sites, including civilian workers at industrial facilities adjacent to the Parchin complex. Tehran’s emergency services chief, Yahya Ali Akbari, told the IRNA news agency that hospitals in the capital had again been placed on a wartime footing.

The Israeli operation unfolded as Iran-aligned militias in Iraq escalated their own campaign against U.S. forces. U.S. Central Command confirmed Saturday that a short-range ballistic missile strike on Camp Taji north of Baghdad had killed six American soldiers and wounded 14 late Friday, and that a separate drone attack on a U.S. logistics convoy near Erbil killed two more service members and three Iraqi contractors early Saturday. Centcom’s running tally, which had stood at 294 on Friday morning, rose to 328 by Saturday afternoon after the Pentagon also confirmed additional deaths from earlier strikes whose details had been withheld pending family notifications.

“Every one of these losses is a wound to this country,” Defense Secretary Pete Hegseth said in a statement issued from the Pentagon. “The president has been crystal clear: the regime in Tehran and its proxies will pay a price commensurate with what they have done to our service members.”

President Donald Trump, who was briefed early Saturday by Hegseth and National Security Adviser Mike Waltz, spoke with Netanyahu twice during the night, the White House said. Press secretary Karoline Leavitt said the United States had “no advance role” in the Israeli strikes but had “coordinated defensive measures” to protect U.S. troops and Gulf partners from anticipated Iranian retaliation. Two senior administration officials, speaking on condition of anonymity, said an additional carrier strike group and two more Patriot batteries were being moved into the Centcom area of responsibility.

In Riyadh and Abu Dhabi, air defenses were placed on heightened alert through the day. Saudi state media reported that Royal Saudi Air Defense Forces intercepted two cruise missiles and a swarm of one-way attack drones launched from Houthi-controlled territory in northern Yemen. The UAE armed forces said its THAAD batteries had intercepted a single ballistic missile over the Empty Quarter. No casualties were reported.

The escalation cast a fresh shadow over the Islamabad talks, where mediators from Pakistan, Saudi Arabia, Egypt and Turkey have spent the past week trying to assemble a ceasefire framework. Pakistani Foreign Minister Ishaq Dar said the talks would continue but acknowledged that “the temperature has risen, and the mediators must rise with it.” An Iranian delegation led by Deputy Foreign Minister Majid Takht-Ravanchi remained in Islamabad, and a senior Saudi diplomat involved in the discussions, speaking on condition of anonymity, said back-channel meetings were now taking place “around the clock.”

“Each side wants to enter any ceasefire from a position of maximum leverage,” said Layla Hassan, a Beirut-based regional analyst with the International Crisis Group. “That is why we are seeing the heaviest fighting of the war alongside the most serious diplomatic effort of the war. They are not contradictions. They are the same logic.”

Brent crude, which had drifted lower through the week after the OPEC+ production hike in Vienna, jumped more than $5 a barrel in early electronic trading before settling near $114 by midday in London. Equity futures in Europe and the United States pointed sharply lower ahead of Monday’s open, with defense and energy shares the only sectors expected to gain.

In Washington, congressional leaders on both sides of the aisle called for closed-door briefings as early as Sunday. Senate Foreign Relations Committee Chairman Sen. Jim Risch (R-Idaho) said in a brief statement that the committee would convene Monday morning. Sen. Chris Murphy (D-Conn.), a leading skeptic of the administration’s war policy, said the latest casualties made it “indefensible” for the Senate to delay further action on a war powers resolution he and a bipartisan bloc reintroduced last week.

Israeli officials said additional operations would be announced in the coming days.