A US soldier in Afghanistan has shot dead 15 civilians and wounded others after entering their homes in Kandahar province, Afghan and Nato sources say.
He reportedly left his base early in the morning to attack village homes. Nine children are among the dead.
The White House said it was "deeply concerned" and Nato-led forces in Afghanistan have begun an inquiry.
Afghan President Hamid Karzai has condemned the attack and demanded an explanation from Washington.
BBC correspondents expect there could be a furious backlash when news of the attack reaches the wider public.
In Kandahar's Panjwai district, local people have reportedly gathered near the base to protest about Sunday's killings, and the US embassy is advising against travel to the area.
Anti-US sentiment is already high in Afghanistan after US soldiers burnt copies of the Koran last month.
US officials have apologised repeatedly for the incident at a Nato base in Kabul but they failed to quell a series of protests and attacks that killed at least 30 people and six US troops.
'My family dead'
The soldier has not been named but is thought to be a staff sergeant.
Quenton Sommerville
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BBC's Quentin Sommerville: "This kind of rogue event is almost unknown in Afghanistan"
He is reported to have walked off his base at around 03:00 local time (22:30 GMT Saturday) and headed to nearby villages, moving methodically from house to house.
Early reports spoke of 16 deaths but Afghan officials later said 15 had been confirmed.
"Eleven members of my family are dead," Haji Samad, an elder from Najeeban village, told AFP news agency.
Haji Sayed Jan, from Alkozai village, said: "My home was attacked and I lost four family members".
Photographs from the scene showed bodies, some of them clearly young children, placed in a vehicle under blankets.
Some reports suggested that more than one soldier was involved in the attack, and a statement by the Taliban accused Afghan security forces of playing a role.
A delegation from the provincial governor's office has arrived in the village to determine exactly what happened, a spokesman said.
The soldier - who reportedly suffered a breakdown before the attacks - is said to have handed himself over to the US military authorities after carrying out the killings.
'Intentional murders'
In a statement, Mr Karzai described the deaths in Kandahar as "intentional murders".
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"When Afghan people are killed deliberately by US forces this action is murder and terror and an unforgivable action," he said.
President Karzai has been consulting officials in Kandahar by telephone. The region is regarded as the birthplace of the Taliban.
Caitlin Hayden, a spokeswoman for the White House National Security Council, said US President Barack Obama had been briefed on the incident. She added: "We are deeply concerned by the initial reports of this incident, and are monitoring the situation closely."
Gen John R Allen, commander of the Nato-led International Security Assistance Force (Isaf), said US officials in Afghanistan would work with their Afghan counterparts to investigate what had happened.
"This deeply appalling incident in no way represents the values of Isaf and coalition troops or the abiding respect we feel for the Afghan people, he said in a statement.
General Carsten Jacobson: "A US soldier left his base in Kandahar in the middle of the night, went into the nearby village, and shot at Afghan civilians"
"I am absolutely dedicated to making sure that anyone who is found to have committed wrong-doing is held fully accountable," he added.
This is the first time Afghan civilians have been targeted by foreign soldiers in this way, the BBC's Quentin Sommerville reports from Kabul.
However, a US soldier was convicted last year on three counts of premeditated murder after leading a rogue "kill team" in Afghanistan.
Kandahar is the Taliban's spiritual heartland and is considered strategically important because of its international airport, its agricultural and industrial output and its position as one of the country's main trading hubs.
The province has seen heavy fighting between Nato and Taliban forces over the last five years.
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Mr Karzai said earlier he still expected to sign a strategic partnership with the US in the next couple of months.
He said discussions would continue on the precise role the US would play in Afghanistan after Nato handed over security responsibility to Kabul at the end of 2014.
On Friday, Kabul and Washington reached a deal to transfer US-run prisons in the country to Afghan control.
