A bomb in Afghanistan's southern Zabul province has killed five Americans - three soldiers and two civilians serving with the Nato-led forces - and an Afghan doctor.
The Nato-led International Security Assistance Force (Isaf) said they were killed when a suicide bomber detonated a car full of explosives.
Another American civilian was killed in an insurgent attack in the east.
Nato is in the process of handing security operations to Afghan forces.
Some areas have already been transferred. Just over 100,000 soldiers are still serving with Isaf; they are due to be withdrawn by the end of 2014.
In Zabul, the suicide bomber blew up his car between a convoy carrying the province's governor and his officials, and a US military convoy. They were passing one another by chance just outside a hospital and a school in the provincial capital, Qalat.
Zabul province is next to Kandahar, and shares a border with Pakistan.
The BBC's Caroline Wyatt in Kabul says provincial Governor Mohammad Ashraf Nasery believes his vehicle was the intended target.
Several other Afghans and Americans were injured in the explosion.
US Secretary of State John Kerry paid special tribute to a state department foreign service officer, who was one of those killed.
He said he had met the officer when she was assigned to support him on his recent visit to Afghanistan.
"She was everything a foreign service officer should be: smart, capable, eager to serve, and deeply committed to our country and the difference she was making for the Afghan people," he said.
"She tragically gave her young life working to give young Afghans the opportunity to have a better future."
Mr Kerry said four state department workers were among the injured, one of whom was critically hurt.
There were no more details of the death of the American in eastern Afghanistan, other than it was "an insurgent attack".
The killings came as Gen Martin Dempsey, chairman of the US Joint Chiefs of Staff, arrived in Afghanistan to see the level of training American troops will give Afghan forces after Nato's combat mission finishes.
The deaths bring the number of coalition military forces killed in Afghanistan so far this year to 30, including 22 Americans and three Britons.