The Taliban claimed responsibility for the convoy attack, which took place near the US military base not far from the airport in Jalalabad, the capital of Nangarhar province.
None of the American soldiers were hurt in the bombing, said Hazrat Hussain Mashraqiwal, the spokesman for the provincial police chief.
The attack happened outside the gates of the base, as a convoy was returning from an early patrol, according to an official at the base who spoke on condition of anonymity because he was not authorized to talk to media.
Taliban spokesman Zabihullah Mujahid says the insurgent group was behind the attack.
The bombing came just two days after an Afghan soldier turned his weapon of American troops at the Nangarhar provincial governor's compound, about 5 kms from the US base.
One US soldier was killed and eight others were wounded in the attack. No group has so far claimed responsibility for Wednesday's attack, which was the first so-called "insider attack" to target NATO troops since they ended their combat mission at the start of the year.
The insurgents have been fighting the Kabul government since the Taliban regime was overthrown by a US-led invasion in 2001. As the weather warms up, attacks from militants moving into Afghanistan across the mountains that border Pakistan are expected to intensify.
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