A US drone attack has hit a militant compound in Pakistan's northwest, the first since a November helicopter strike killed 24 Pakistani soldiers and triggered a crisis in relations.

Four militants were killed late Tuesday when two missiles struck the compound on the outskirts of Miranshah in North Waziristan, a lawless tribal region near the Afghan border, security officials said.

The attack set the building on fire and flames could be seen from the roofs of houses in Miranshah, which lies five kilometres (three miles) away, residents reported.

The drone attack, which was confirmed by two other security officials, was the first since the November 25-26 helicopter attacks on a Pakistan border checkpoint.

The incident triggered outrage in Pakistan and aggravated tensions in an already shaky relationship, prompting Islamabad to block crucial NATO supply convoys to Afghanistan.

A joint US-NATO investigation concluded last month that a disastrous spate of errors and botched communications led to the deaths.

It said that both sides failed to give the other information about their operational plans or the location of troops and that there was inadequate coordination by US and Pakistani military officers.

Brigadier General Stephen Clark, who led the probe, said the episode reflected "an over-arching lack of trust between the two sides as far as giving out specifics".

Pakistan rejected the results of the coalition's investigation and insisted the strikes had been a deliberate act of aggression.

The US drone campaign has killed dozens of Al-Qaeda operatives and hundreds of low-ranking fighters in Pakistan since the first Predator strike in 2004, but the programme has infuriated many Pakistanis.

The Los Angeles Times reported last month that the US Central Intelligence Agency had suspended drone strikes on gatherings of low-ranking militants in Pakistan due to the tensions caused by the campaign.

The latest drone strike came on the same day that a remote-controlled bomb blast killed 35 people and wounded more than 60 others in the troubled Khyber tribal region of northwest Pakistan.

The region had served as the main supply route for NATO forces operating in Afghanistan before the suspension triggered by the November incident.

There was no immediate claim of responsibility for the bombing but local residents suggested it was a tribal dispute.

The United States denounced the blast, which struck in a marketplace.

"By callously targeting innocent peoples, the extremists who planned and perpetrated this attack are just showing their contempt for the value of human life," State Department spokeswoman Victoria Nuland said.

"We remain deeply committed to working with Pakistan to address these kinds of terrorist threats and the results of violent extremism," she said, adding that the US could not confirm reports that Al-Qaeda was behind the attack.

The border crossing for supplies to foreign troops fighting in Afghanistan remains closed and NATO said this month that it wants to get relations with Pakistan back on track "as quickly as possible" so it can be reopened.