The drone targeted a house 3 km (2 miles) east of Miranshah, the main town of the region, known to be a hotbed of Taliban and al Qaeda militants.

It was not immediately known if any high-profile militants were among the dead. Militants often dispute official account of such strikes.

Initial reports said five militants were killed in the attack but officials said the toll had gone up to 21 after more bodies were found from the rubble of the house.

Drone strikes have been a major source of friction between the US and Pakistan, with ties at their worst since US Special Forces killed al Qaeda chief Osama bin Laden in a secret raid in a Pakistani garrison town in May.

While Pakistan publicly opposes the strikes, it has privately allowed them and cooperated with the US determining targets.

But since the May commando raid, which Pakistan considers a grievous breach of sovereignty, the powerful head of the army, General Ashfaq Kayani, has called for a halt.

Washington appears determined to press forward with drone attacks, which its sees as an effective tool to stem cross-border attacks by militants on foreign forces in Afghanistan.