Fighter planes have hit Iranian-backed militia positions near the Syrian border with Iraq, according to activists.
The Syrian Observatory for Human Rights, a UK-based surveillance group, said at least 18 Iranian and pro-Iranian fighters were killed.
It was not clear who carried out the nightly strikes in and around the city of Albu Kamal.
But Israel has carried out hundreds of attacks on Iranian-linked targets in Syria during the country's civil war.
An attempt was made to thwart Iran's so-called "military anchoring" in Syria and the shipment of Iranian weapons to militant groups such as Hezbollah in Lebanon.
The Syrian Human Rights Observatory reported that the unidentified Combat aircraft bases, weapons depots and vehicles were bombed by Les, who belonged to Iranian-backed militias in al-Hizam al-Akhdar and other areas around Albu Kamal.
Omar Abu Layla, a European-based activist from the DeirEzzor 24 group, said massive explosions were heard throughout the city. "Militia fighters were in a state of chaos and panic."
Another activist group, Sound and Picture, reported from medical sources that 21
A source of the Iran-backed Iraqi paramilitary force, the Popular Mobilization, told the BBC that a drone had attacked its headquarters on the Iraqi-Syrian border, about 6 km south of Albu, Kamal.
The force had sent vehicles from the nearby Iraqi city of al-Qaim to the scene because of the large number of victims, the source added.
Hours later, a series of rockets fired from Israel on the outskirts of the Syrian capital Damascus us, but failed to hit Israeli territory, according to the Israeli military.
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It accused militia fighters operating under the command of the Quds Force of the Iranian Revolutionary Guards, but said that it blamed the Syrian government.
Meanwhile, Hezbollah said its fighters shot and captured an unmanned Israeli drone over southern Lebanon early Monday.
The Israeli military said one of its drones had "fallen into southern Lebanon during routine operations." There was no reason, but said there that "no objections can be derived from it".