State TV quoted a local security official as saying the plane had crashed about 65 kilometres (40 miles) from the city of Konarak in Iran's southern Sistan-Baluchistan province.
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"Unfortunately a military training aircraft crashed today due to technical problems," killing the pilot and co-pilot, Ali Asghar Mirshekari, the provincial deputy security chief, told the channel.
No other details were provided on the possible cause of the crash.
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Another Iranian F-4 fighter crashed near the city of Shiraz in July 2014, leaving both pilots dead.
The Iranian Air Force continues to operate several F-4s bought from the United States before Iran's 1979 Islamic revolution.
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