Two Americans and two Pakistanis working at the U.S. Consulate in Peshawar were among the wounded, said a U.S. Embassy official, speaking on condition of anonymity because an official statement had not yet been issued.
Peshawar is located near Pakistan's semiautonomous tribal region, the main sanctuary for Taliban and al-Qaida militants in the country. The city has been hit by scores of bombings in recent years, but attacks against American targets are relatively rare because of the extensive security measures taken by the U.S. government.
The vehicle was attacked after it left the U.S. Consulate in Peshawar and was traveling through an area of the city that hosts various international organizations, including the United Nations, said police officer Pervez Khan, who was part of the security escort for the vehicle as it moved.
The attack killed two Pakistanis and wounded 19 other people, said senior police officer Javed Khan. A U.S. passport was found in the wreckage of the vehicle that was attacked, he said.
Local TV footage showed an SUV at the site that was completely destroyed and burned. All that was left was a carcass of blackened, twisted metal. Pervez Khan said the images were of the U.S. vehicle that was attacked.
A police explosives expert, Abdul Haq, said 110 kilograms (240 pounds) of explosives were used in the attack.
Irfan Khan, a local resident, said he was at a nearby shop when the blast occurred.
"I quickly looked back in panic to see smoke and dust erupt from the scene," said Khan. "I ran toward the scene along with others and saw two vehicles destroyed and the larger vehicle on fire."
One dead person was on the ground near the SUV, and a foreigner was injured, said Khan.
"We put the injured man and the dead body in a private vehicle," said Khan. "There were more injured in the surrounding area too."
Another eyewitness, Wajid Ali, said he helped put another seriously injured foreigner into the vehicle.
But another vehicle arrived, presumably from the U.S. Consulate, and took away the injured foreigners, said Javed Khan, the police officer.
Some of the policemen escorting the U.S. vehicle were also wounded in the attack, and their vehicle was damaged, said Khan.