A suicide attack on a joint Afghan-NATO foot patrol on Monday killed at least 14 people, including three NATO troops and an interpreter, officials said.
Four Afghan police and six civilians were also killed, and 37 were wounded in the attack near a market in the eastern city of Khost, the provincial governor's office said.
Taliban insurgents claimed responsibility for the blast.
"Today at around 8:30 am (0400 GMT) a suicide bomber on a motorcycle targeted a joint patrol in Khost city in a crowded area.
"In this inhuman attack three police and 37 civilians were wounded, and six civilians and four police, including the commander of the quick reaction forces, were killed," the governor's office said in a statement.
Hospital sources put the number of Afghan dead at 10 with more than 60 wounded.
NATO's US-led International Security Assistance Force confirmed that three NATO service members and an ISAF-contracted interpreter had been killed in the attack.
The Taliban Islamists said on their website that the suicide attack was carried out by "a hero mujahid, Shohaib, from Kunduz", claiming that eight foreigners and six Afghan soldiers were killed.
The deaths take coalition casualties to at least 347 this year, according to an AFP tally.
NATO has more than 100,000 troops fighting a Taliban insurgency in Afghanistan, but they are due to pull out by the end of 2014.
Joint NATO-Afghan operations have been temporarily restricted since last month after a spike in insider attacks, in which Afghan security forces turned their weapons against their coalition allies.
The latest blast came a day after NATO announced that a firefight between coalition troops and their Afghan allies killed an ISAF soldier, a civilian contractor and three Afghan army troops in circumstances that remained murky.
The incident was initially described as a suspected insider attack, but it was later suggested that either insurgent fire or a verbal argument between the troops sparked the shooting.
At least 51 coalition troops have been killed in insider assaults this year -- about 15 percent of all NATO deaths -- and the top ISAF general has described them as "the signature attack" of the Afghan war.
The scale of the insider assaults is unprecedented in modern warfare, and has seriously undermined trust between NATO coalition forces and their Afghan allies in the joint effort against Taliban insurgents.
"I'm mad as hell about them, to be honest with you," ISAF commander General John Allen told CBS's "60 Minutes" programme recorded before the latest incident and aired Sunday.
"We're willing to sacrifice a lot for this campaign, but we're not willing to be murdered for it," the commander said.
NATO says that overall insurgent attacks on its forces dropped by five percent in the first eight months of this year compared to 2011, but are still running at about 100 a day.
It said the decline in attacks showed that its troops had been able to "reverse the momentum" of the insurgents' campaign, an interpretation that the Taliban "strongly and categorically" denied.
According to the United Nations, August was the second deadliest month in five years for civilians, with a total of 374 -- more than 10 a day -- killed and 581 injured.