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It was not known whether the three were security contractors or some of the many other types of contractors currently working in Iraq, officials said.
One U.S. official said the disappearance is being treated as "a possible kidnapping," but the official was not aware of any reports of anyone witnessing that.
A separate senior U.S. official said that every indication they have is that the three Americans went missing south of Baghdad two days ago.
A State Department spokesman said it was working with Iraqi authorities to find the three.
"We are working with the full cooperation of the Iraqi authorities to locate and recover the individuals," State Department spokesman John Kirby said. "Due to privacy considerations, I have nothing further."