Local officials say US missiles on Thursday killed one of the most senior al-Qaeda militants in Pakistan, Badar Mansoor.
The al-Qaeda chief, Badar Mansoor is suspected of killing dozens of people in attacks in Pakistan and further afield.
The US drone strike took place in Miranshah in North Waziristan tribal area, close to the border with Afghanistan.
US President Barack Obama has defended the use of drones to target militants in Pakistan’s tribal areas.
If Badar Mansoor’s death is confirmed, his demise would be seen by the US as a vindication of its drone programme, correspondents say.
He is thought to have trained new fighters and planned numerous suicide attacks, including one against Pakistan’s Ahmadi Muslim minority in Lahore in which about 90 people died, our correspondent adds.
Al-Qaeda has so far not publicly commented on the claim, but AFP news agency has quoted one Mansoor loyalist confirming the death.
Pakistani officials say he was among at least four militants killed in the pre-dawn strike.
The drone attack was the second in North Waziristan in as many days. On Wednesday, 10 suspected militants were killed, Pakistani security officials said.
Drone attacks cause huge anger in Pakistan, which has previously complained that they violate its sovereignty. However, correspondents say the authorities are believed privately to give their support to the US for the attacks.
The US does not normally comment on drone operations, which have killed hundreds of people in recent years. The dead include senior al-Qaeda and Taliban leaders, as well as an unknown number of other militants and civilians.