USA officials say American advisors accompanying Syrian opposition forces came under attack by government-backed troops in Deir el-Zour Province.
The statement was very light on details, but accused pro-Syrian forces of attacking the "headquarters" of the Syrian Defense Forces, where United States troops were stationed.
Syrian state media said the USA -led coalition bombing had left dozens killed and wounded.
Assad regime forces hit the headquarters of the Syrian Democratic Forces.
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The flare-up lasted into the small hours of Thursday and was sparked by an attack on positions held by the Kurdish-led Syrian Democratic Forces (SDF) in Deir Ezzor province.
Neither U.S. officials nor the U.S. -backed coalition have offered details on the identity of attacking forces.
Overall, the pro-government force included about 500 people supported by rocket and mortar systems and Soviet-era tanks, the official said.
"The coalition conducted strikes against attacking forces to repeal the act of aggression", it said.
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About 100 of the attackers were then killed in a counter-strike, an American military official said. Officials declined to say whether the airstrikes were conducted with manned or unmanned aircraft.
More than 100 fighters aligned with Syrian President Bashar al-Assad were killed overnight when US coalition and coalition-backed local forces repelled their attack in eastern Syria, a USA official said on Thursday.
Regime and SDF fighters were involved in several skirmishes in the area a year ago, as they each conducted parallel operations against some of the Islamic State jihadist group's last bastions. One SDF member was injured.
Another military official, who also spoke on the condition of anonymity, said not all the attacking forces were wearing uniforms, making it more hard to identify them.
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