A US drone strike in Pakistan on Wednesday killed up to 21 Afghan fighters from the Al-Qaeda-linked Haqqani network, considered the top US foe in eastern Afghanistan, authorities said.

Pakistani officials said a US drone fired two missiles, destroying a vehicle and a compound in North Waziristan, the headquarters of the Haqqani leadership and the most infamous militant bastion in the semi-autonomous tribal belt.

"More dead bodies have been dug out of the debris. Twenty-one militants from the Haqqani group were killed and three were injured," a Pakistani security official told AFP in Peshawar, the largest city in the northwest.

"All those killed in the strike were Afghans and Haqqani's fighters," he added, speaking on condition of anonymity because he was not authorised to speak to the media.

Although the United States does not publicly confirm Predator drone attacks, its military and the CIA in Afghanistan are the only forces that deploy the armed, unmanned Predator aircraft in the region.

Washington has called Pakistan's semi-autonomous northwest tribal region the global headquarters of Al-Qaeda, where Taliban and other Al-Qaeda-linked networks need to be defeated if the 10-year war in Afghanistan is ever to end.

The Haqqani network is considered the most dangerous enemy of US troops in eastern Afghanistan. It was founded by Jalaluddin Haqqani and is run by his son, Sirajuddin, both designated "global terrorists" by Washington.

The group has been blamed for some of the deadliest anti-US attacks in Afghanistan, including a suicide attack at a US base in the eastern province of Khost in 2009 that killed seven CIA operatives.

Pakistani officials said the missiles struck what was reportedly a Haqqani training camp at 2:15 am (2115 GMT Tuesday) close to Miranshah, the main town in North Waziristan.

Some Pakistani officials put the death toll at 18 but acknowledged that more bodies were being dug out of the rubble.

The officials said a pick-up vehicle parked outside the compound was also destroyed.

"The vehicle was hit minutes after it reached the house. It looks like the drone was chasing it. One missile hit the vehicle and another hit the house. Four militants sitting in the vehicle were also killed," one official said.

Local residents in Miranshah reported hearing two huge blasts a minute apart as they were waking up for a night-time meal to help them get through the dawn-to-dusk daily fast of the holy month of Ramadan.

One resident told AFP that he later saw 16 coffins laid out in the back of vehicles, which were then taken to a nearby graveyard.

Around two dozen drone strikes have been reported in Pakistan since elite US forces killed Al-Qaeda chief Osama bin Laden in a suburban home near Pakistan's main military academy in Abbottabad, close to the capital, on May 2.

The raid humiliated Pakistan and prompted allegations of incompetence and complicity in sheltering bin Laden.

Pakistan is seen as a key ally for the United States in its fight against Islamist militancy, but relations have soured since the bin Laden raid, carried out without, apparently, pre-warning Islamabad.

Drone attacks are unpopular among many Pakistanis, who oppose the alliance with Washington and who are sensitive to perceived violations of sovereignty.

US officials have accused Pakistani intelligence of playing a double game with extremists, including the Afghan Taliban and the Haqqani network, in order to exert influence in Afghanistan and offset the might of arch rival India.

US pressure on Islamabad to launch a decisive military campaign in North Waziristan, as Pakistan has conducted elsewhere in the tribal belt, has so far fallen on deaf ears.