An Iran-backed terror group has claimed to have shot down an American military plane over Iraq - which the US denies.
The Islamic Resistance in Iraq, a network of Iran-backed backed Shia Islamist groups, claimed it downed the plane in "defence of our country's sovereignty and airspace" on Thursday.
US Central Command said the crash involved another aircraft but was not the result of hostile or friendly fire.
Rescue efforts are underway for the KC-135 refuelling aircraft's six missing crew.
The second aircraft, also believed to be a KC-135, landed safely.
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"The incident occurred in friendly airspace during Operation Epic Fury," a Centcom statement said.
Officials are working to gather additional details and provide clarity for the families of service members, officials said.
The statement in full reads: "US Central Command is aware of the loss of a US KC-135 refuelling aircraft.
"The incident occurred in friendly airspace during Operation Epic Fury, and rescue efforts are ongoing. Two aircraft were involved in the incident. One of the aircraft went down in western Iraq, and the second landed safely.
"This was not due to hostile fire or friendly fire.
"More information will be made available as the situation develops. We ask for continued patience to gather additional details and provide clarity for the families of service members."
The KC-135 refueling aircraft was lost (file pic)
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The plane, known as the Stratofortress, is believed to be the fourth American aircraft lost during Operation Epic Fury, after three F-15s were shot down in friendly fire over Kuwait.
KC-135s, which have been in service for over six decades, tend to have a crew of three, but can carry up to 37 passengers.
Since the US and Israel started carrying out strikes against Iran on February 28, seven US troops have been killed.
Reuters reported on Tuesday that as many as 150 US troops have been wounded in the US-Israeli war on Iran.
Iran's total death toll reported by its state media on Monday stood at at least 1,270 people.
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Smoke and flames rise at the site of airstrikes on an oil depot in Tehran
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However, Iran's ambassador to the United Nations said on March 6 that at least 1,332 people had been killed since the war began. There has been no clarification of the discrepancy.
It was not clear if those figures include at least 104 people that the Iranian military said were killed in a US attack on an Iranian warship off Sri Lanka's coast on March 4.
In Lebanon, at least 687 people have been killed in Israeli strikes, according to Lebanese authorities. The World Health Organization said at least 98 of those killed were children.
At least 30 people have been killed in Iraq, according to local health authorities. Most of those were members of the Shi'ite Popular Mobilisation Forces.
Missiles launched from Iran in retaliation for Israeli attacks are seen in the night sky over the city of Hebron in the West Bank
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In Israel, 12 people have been killed, including nine people in an Iranian missile strike on Beit Shemesh near Jerusalem on March 1, according to Israel's ambulance service Magen David Adom.
The military said two soldiers were killed in southern Lebanon, the first fatalities among its troops since hostilities with Hezbollah resumed last week.
Israeli Prime Minister Benjamin Netanyahu said Iran was "no longer the same" after nearly two weeks of joint US-Israeli attacks and had suffered blows to its elite forces.
Appearing in his first press conference since the start of the war, Mr Netanyahu said he spoke with Mr Trump nearly every day and that the two men spoke "openly" about the war.
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