A commander in the regional alliance backing Syrian President Bashar Assad said the drone was engaged in operations in southern Syria when it was targeted by an Israeli anti-aircraft missile.
Earlier, residents of the Upper Galilee in Israel's north reported hearing an explosion and seeing a smoke trail in the sky.
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The incident comes after the Syrian army and allied forces pounded rebel-held areas in the strategic region bordering Jordan and the Golan Heights.
The bombings were supported by Russian aircraft, marking the first time in a while that Russian aircraft attacked targets so vigorously in southern Syria.