The attack in the Khyber region was the bloodiest in Pakistan this year and came hours before President Barack Obama was due to unveil a revised strategy expected to emphasize the need to eradicate militant havens along the Pakistan-Afghan frontier.
A government official accused Islamist militants of carrying out the bombing in revenge for a recent offensive aimed in part at protecting the major supply route for NATO and U.S. troops in Afghanistan that passes in front of the mosque.
"Residents of this area had cooperated and helped us a lot. These infidels had warned that they will take revenge," said Tariq Hayat, the top administrator of the Khyber tribal region. "They are the enemy of Pakistan. They are the enemy of Islam."
Rising violence in Pakistan is fueling doubts about the pro-Western government's ability to counter Taliban and al-Qaida militants also blamed for attacks on Western troops in Afghanistan.
The bomber hit the mosque, a popular stop for travelers motoring between Pakistan and Afghanistan, when about 250 people were attending Friday prayers, said Hayat.
Television footage showed scores of residents and police officers digging frantically with their hands through the ruins of the white-walled mosque, whose roof collapsed in the explosion.
Rescuers hauled bodies covered in dust and blood on blankets and scarves toward ambulances and private cars waiting to take them to hospital. Crowds of anguished women waited in the background, hoping for news of loved-ones.
Hayat said rescuers had pulled 48 bodies from the rubble and predicted the toll would likely rise further. Another 80 people were injured, he said.
The mosque in a rocky valley near the town of Jamrud lies on the main road along which trucks carry vital supplies to the expanding U.S.-led force in Afghanistan.
Suspected Taliban militants have carried out a string of attacks on both trucks and transport depots along the route in recent months, destroying scores of military vehicles, including Humvees, raising doubts about the reliability of the supply line.
The area has also been beset by feuds between rival tribal and militant groups, some of them loosely allied with the government, which have included suicide bombings and attacks on mosques.
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