The vehicle was hit by the blast near the main southern city of Kandahar. A local Afghan police chief said it was a suicide assault. The U.S. military confirmed it was a bombing, but gave no further details.
Spokesman Col. James Yonts told reporters in Kabul that the four wounded, one in a serious condition, were flown to a U.S. base in Kandahar for medical treatment.
"A preventional reconstruction team was traveling outside of Kandahar when an IED exploded," Yonts said. "It is a sad day when coalition forces supporting the Afghan people inside of Kandahar are attacked by someone in this nature."
Gen. Salim Khan, the deputy police chief for Kandahar city, said a suicide bomber had rammed a car full of explosives into the U.S. vehicle. The head of the attacker was found near the site of the blast and it appeared to be that of an Arab, he said.
"The U.S. vehicle was blown up in the suicide attack," Khan said.
He said at least three American troops were killed, but in a statement, the U.S. military said no U.S. service members had died.
An Associated Press reporter at the scene saw three American soldiers being carried on stretchers into a U.S. military helicopter. Two other U.S. helicopters hovered overhead, while dozens of Afghan and U.S. troops took up positions around the site.
Troops blocked the highway where the attack happened. The road links Kandahar and the western city of Herat. Hundreds of Afghans who had been driving along the road looked on.