The 20-vehicle-convoy was carrying US Special Forces along the road linking Khost and Paktia provinces when they came under AK-47 assault rifle and rocket-propelled grenade attack, said a US military spokesman on Thursday.
The assailants fled the area after fighting, but it was unclear whether there were any casualties among the attackers.
The attacks come as the US' aim of establishing a strong central government in Afghanistan suffered another setback.
About 80 Afghan fighters were killed or wounded in one of the worst outbreaks of fighting between pro-government factions since the Taliban were ousted almost two years ago.
The ethnic Uzbek faction of General Abd al-Rashid Dostum overran several districts west of the northern capital of Mazar-e-Sharif in fighting involving tanks, artillery and mortars that began on Wednesday and continued overnight, said the rival Tajik faction.
General Abd al-Saboor said at least 60 members of the Tajik Jamiat faction of Atta Muhammad had been killed or wounded, but he gave no breakdown. Uzbek, Junbish officials said at least three of its soldiers were killed and four others hurt.
“Around Mazar-i-Sharif the situation is not good,” Interior Minister Ali Ahmad Jalali told reporters.
Suspected Taliban fighters have
been captured in recent sweeps
Jalali will lead a delegation to Mazar on Thursday, aimed at easing tensions and implementing military and administrative reforms.
Fighters from the two factions have clashed repeatedly since the Taliban were ousted by US-led forces in late 2001. Past UN-disarmament drives have failed.
The violence has raised doubts about the ability of President Hamid Karzai’s government to bring stability to the entire country.
The latest fighting erupted as the Defence Ministry, United Nations and Japan signed an agreement on Wednesday to demobilise 100,000 factional fighters.
A spokesman for the world body, which runs aide programmes from Mazar-e-Sharif, said the fighting was one of the worst seen in the north and was of “great concern”.
Jalali said he had spoken to the leaders of the fighting factions, Dostum and General Atta Muhammad. Both are government officials and pledged to defuse the situation, which they blamed on incidents at a “lower level”.