Three US service members have been killed and at least 34 wounded in a drone attack by Iran-backed militants on US troops in northeastern Jordan near the Syrian border, President Joe Biden and US officials say.
It's the first deadly strike against US forces since the Israel-Hamas war erupted in October and marks a major escalation in tensions that have engulfed the Middle East.
"While we are still gathering the facts of this attack, we know it was carried out by radical Iran-backed militant groups operating in Syria and Iraq," Biden said in a statement on Sunday.
"Have no doubt - we will hold all those responsible to account at a time and in a manner of our choosing."
Iran's mission to the United Nations said in a statement on Monday that Tehran was not involved in the attack.
"Iran had no connection and had nothing to do with the attack on the US base," the mission said in a statement published by the state news agency IRNA.
"There is a conflict between US forces and resistance groups in the region, which reciprocate retaliatory attacks."
Biden asked for a moment of silence for the three killed service members during a campaign event in South Carolina, adding: "We shall respond."
US Defense Secretary Lloyd Austin echoed that threat, adding he was "outraged and deeply saddened" by the attack.
He and other senior officials briefed Biden earlier in the day.
At least 34 personnel were injured in the attack, but that number is expected to change as more people seek care, according to US Central Command.
Eight personnel were taken from Jordan for higher level care but are in stable condition.
Two US officials said the drone struck near the barracks early in the morning, which could explain the high number of casualties.
The Islamic Resistance in Iraq, an umbrella organisation of hardline Iran-backed militant groups, claimed attacks on three bases, including one on the Jordan-Syria border.
The attack is likely to fan fears of wider conflict in the Middle East, where war broke out in Gaza after Palestinian Islamist group Hamas' attack on Israel on October 7 that killed 1200.
Israel's subsequent assault on Gaza has killed over 26,000 Palestinians, according to the local health ministry.
Since then, US forces have come under attack more than 150 times by Iran-backed groups in Iraq and Syria, causing at least 70 casualties prior to Sunday's attack, most of them traumatic brain injuries.
US warships have also been fired at by Iran-backed Houthi forces in Yemen, who are regularly attacking commercial ships passing through Red Sea waters off Yemen's coast.
While the United States has maintained an official line that Washington is not at war in the region, it has been retaliating against the Iran-backed groups in Iraq and Syria and carrying out strikes against Yemen's Houthi military capabilities.
A senior official with the Iran-backed Palestinian militant group Hamas, Sami Abu Zuhri, directly tied the attack to Israel's campaign in Gaza.
"The killing of three American soldiers is a message to the US administration that unless the killing of innocents in Gaza stops, it must confront the entire nation," he told Reuters.
"The continued American-Zionist aggression on Gaza is capable of exploding the situation in the region."
The US military said the attack occurred at a base in northeastern Jordan, near the Syrian border.
It did not name the base, but a person familiar with the matter identified it as Tower 22 in Jordan.
US military activity in Jordan can be a sensitive issue, particularly at a time of heightened tensions due to the Israel-Hamas conflict, because of increasing concern in Jordan about the war spreading.
The Jordanian government said only that the attack occurred at an "advanced post" along its border with Syria.