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Central Command gave no details of the plane's mission, and said the cause of the crash and the condition of the pilot were currently unknown.
"The specific location is not releasable due to host nation sensitivities," US Air Force Capt David W Small, a Central Command spokesman, told the news agency.
AP says south-west Asia is a phrase often used by the US military to refer to the Middle East.
BAGHDAD, Iraq - A U.S. Air Force U-2 spy plane involved in a mission in
Afghanistan crashed while returning to its base in the United Arab Emirates, killing the pilot, the military said Wednesday.