At least eight women have died in a Nato air strike in Afghanistan's eastern province of Laghman, local officials say.
Nato has conceded that between five and eight civilians died as it targeted insurgents, and offered condolences.
Afghan President Hamid Karzai "strongly condemned" the deaths and has sent officials to the area to investigate.
Earlier on Sunday, four US soldiers with the Nato forces were killed in an attack by suspected Afghan police.
The attack in southern Zabul province brought to 51 the number of Nato troops killed in "insider attacks" this year, and came a day after two UK soldiers were killed at a checkpoint in Helmand by a man in police uniform.
Local officials in the remote area of Laghman told the BBC at least eight women had died, while provincial council member Gulzar Sangarwal said nine were dead.
Major Adam Wojack, a spokesman for the Isaf international forces, said between five and eight civilians could have been killed, and said an investigation was under way.
He told the BBC that a group of some 45 insurgents had been targeted by an Isaf unit, and many had been killed.
"Unfortunately, we have become aware of possible Isaf-caused civilian casualties as a result of this strike, numbering five-eight Afghans," he said.
"Isaf offers its sincerest condolences to the affected community and family members, as well as to the Afghan people, concerning this tragic loss of life."
At least seven women were also reported to have been injured. Provincial health director Latif Qayumi said some of them injured were girls aged as young as 10.
The Laghman governor's office said a number of civilians had gone to the mountains to collect wood and nuts from a forest in the Noarlam Saib valley, a common practice in the area.
The mountainous, highly forested terrain remote from government control make the area attractive to Taliban and other insurgent groups, correspondents say.
The issue of civilian deaths by international forces has created tensions between the US President Karzai.
In August, UN figures suggested the number of civilians killed and injured in the first half of 2012 had fallen 15% on the same period of 2011.
Analysts said increased sensitivity on both sides about the impact of civilian deaths had led to more carefully targeted attacks.
In his statement, Mr Karzai expressed his "sorrow" over the incident, saying he "strongly condemns the airstrike by Nato forces which resulted in the deaths of eight women".
Isaf spokesman Lt Col Hagen Messers said the remote base in Zabul province came under attack in the early hours of the morning, AFP reports.
The US troops were scrambled to help the Afghans repel the attack, but four of them were shot dead by Afghans in police unfirm
Officials said it was not yet clear whether the attacker or attackers were genuine police, but one provincial office told AFP that three or four known policemen had since disappeared from the base.
"At the moment, we don't know where they have gone. We don't know if they fled fearing arrest or if they are linked to the Taliban," he said.
Zabul's deputy police chief Ghulam Gilani told the Associated Press the police could have been forced into attacking the American troops.
"Whether they attacked the Americans willingly we don't know," he said.
Meanwhile, more details have also emerged of the scale of damage caused by an insurgent attack on Nato's heavily fortified Camp Bastion base in Helmand province, in which two US marines were killed.
Militants breached the perimeter of the sprawling base in Helmand province, destroying six US Harrier aircraft and damaging two more, destroying three refuelling stations and damaging six aircraft hangars.
Nato said 14 of the insurgents were killed and one was injured and taken into custody. Nine coalition personnel were wounded.
In a statement, Nato said the attack had been carried out by 15 insurgents dressed in US Army uniforms who "appeared to be well-equipped, trained and rehearsed".