An American soldier walked off his base in southern Afghanistan and opened fire on civilians on Sunday, reportedly killing three, Western and Afghan officials said.
The soldier was held afterwards, NATO's International Security Assistance Force (ISAF) said in a statement.
"A United States service member was detained today in connection to an incident that resulted in Afghan casualties in Kandahar province," it said, without specifying the number of victims.
A Western official told: "A soldier walks off the base (in the early hours of Sunday morning) and starts shooting. He got back to the office and was detained."
The governor of Kandahar province said three people were reportedly killed.
"Our initial information indicates that three people are dead but we don't know who they are," said governor Toryalai Wesa, adding that an investigation was under way.
The shooting comes after a series of incidents in which Afghan soldiers turned their weapons on American troops, killing six, after Korans were burned at a military base.
But there was no word on what might have motivated the soldier's actions.
"This is a deeply regrettable incident and we extend our thoughts and concerns to the families involved," ISAF said.
"US Forces-Afghanistan (USFOR-A), in cooperation with Afghan authorities, will investigate this incident and release additional information as appropriate."
The Koran burning ignited days of violent anti-US protests in which some 40 people died, plunging relations between foreign forces and their Afghan allies to an all-time low and forcing US President Barack Obama to apologise.
NATO withdrew all its advisors from Afghan government ministries after two American officers were shot and killed inside the interior ministry, apparently by an Afghan colleague, following the burning.
Of the 60 NATO troops killed so far this year, 18 per cent - almost one in five - have died at the hands of Afghan colleagues, including four French and an Albanian, as well as the six Americans.
The US has a strong presence in Kandahar, the birthplace of the hardline Islamist Taliban which is waging an insurgency against the government of President Hamid Karzai.
The US leads some 130,000 NATO troops in Afghanistan in defence of the Karzai government.