American forces in Syria launched “self-defence” artillery strikes on Monday after they were hit by a barrage of rockets, a US military spokesman said.
The exchange of fire came a day after the Pentagon conducted three strikes it said were aimed at pro-Iran groups in eastern Syria and western Iraq.
A US military spokesman said there were no injuries in Monday evening's attack.
The Syrian Observatory for Human Rights said pro-Iranian militias fired several shells at a US base in eastern Syria's Al Omar oil field on Monday night, causing damage but no casualties.
Syrian state news agency Sana said "missiles targeted a military base of the US occupation forces in Al Omar oilfield", without saying who was responsible.
The US military has a base in the town of Deir Ezzor and video on social media appeared to show militants launching rockets at the site, which houses the 900 US troops who remain in the country.
In response, US forces fired "heavy artillery" on the nearby town of Al Mayadeen, controlled by Iranian-backed militias, the Syrian Observatory reported.
The US military spokeman confirmed that American troops "acted in self-defence" by firing artillery at militia targets.
Earlier on Monday, officials from the administration of Joe Biden continued to defend Sunday's air strikes on Iran-backed militias in Iraq and Syria.
US Secretary of State Antony Blinken said they showed the US would not hesitate to protect its interests in the Middle East.
Sunday's attacks, which killed four fighters and aimed at sites used to launch drone attacks, should “send a clear and unambiguous deterrent message", Mr Blinken said on Monday during a visit to Rome.
“I hope very much that it is received by those who are intended to receive it,” he said.
Sunday's air strikes were in response to attacks on US interests and were a “necessary, appropriate and deliberate action” designed to limit the risk of escalation, Mr Blinken said.
The strikes on Sunday hit two sites in Syria and one in Iraq.
The US has said they were aimed at deterring future attacks on American interests in Iraq, where it is aiding government efforts to defeat ISIS.
“The attacks on our troops need to stop,” White House press secretary Jen Psaki said on Monday.
She spoke of at least five attacks since April using drones with weapons as the reason behind the air strikes.
The armed drones increasingly being used by the militias are more accurate and harder to detect and shoot down than rockets.
Agencies contributed to this report