The nature of the blast, which occurred at Pashat in Bajaur region at 10.50 am, could not immediately be ascertained.
Malik Mian Jan and Malik Tahsin Khan, two tribal elders associated with an anti-Taliban `lashkar` or militia, were killed by the blast, officials said.
The injured were taken to a hospital in Khar, the main town of the region located 65 km from Salarzai.
Security forces cordoned off the site of the blast and launched a search operation. The blast targeted Malik Mian Jan`s hotel, where he was meeting other tribal elders, witnesses said.
No group has claimed responsibility for the blast. The Taliban have killed dozens of pro-government tribesmen and members of anti-militant militias in the tribal belt over the past few years.
Leaders of the anti-Taliban militia in Bajaur Agency had been threatened by the Taliban, local residents said.
Bajaur Agency, which borders Afghanistan, was a stronghold of Taliban militants who were expelled by security forces in 2008-09.