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Pakistan's army chief has condemned the latest raid by US unmanned drones as "intolerable and unjustified".
In a strongly worded statement, Gen Ashfaq Pervez Kayani said the attack, which killed about 40 people, was "in complete violation of human rights".
Most of the victims were believed to be civilians attending a tribal meeting near North Waziristan's regional capital, Miranshah.
Tension has been growing in recent weeks between the US and Pakistan.
The US drone attacks are a long-running source of bad feeling, but the acquittal of CIA contractor Raymond Davis of murder has sparked protests across Pakistan.
The Pakistani military often makes statements regretting the loss of life in such incidents, but rarely criticises the attacks themselves.
Gen Kayani, however, said such "acts of violence" make it harder to fight terrorism.
"It is highly regrettable that a jirga [meeting] of peaceful citizens including elders of the area was carelessly and callously targeted with complete disregard to human life," he said.
"It has been highlighted clearly that such aggression against people of Pakistan is unjustified and intolerable under any circumstances."
Pakistan's intelligence agency is often accused of complicity in the raids, either by supporting them or allowing them to happen.
The BBC's M Ilyas Khan in Islamabad says Thursday's drone strike is thought to have killed more civilians than any other such attack since 2006.
Officials say two drones were involved in the latest attack, in the Datta Khel area 40km (25 miles) west of Miranshah.
One missile was fired at a car carrying suspected militants. Local tribesmen say the drones then fired another three missiles at their open-air meeting, or jirga.
Our correspondent says the car was moving close to the jirga, and the missiles hit the vehicle as well as the jirga.
According to the tribesmen, the meeting was being held to discuss a local land dispute over the ownership of chromite deposits in the area. They say that no militants were present at the time.
Officials said the drones were targeting militants linked to Taliban commander Hafiz Gul Bahadur. One of his commanders, identified as Sharabat Khan, was in the vehicle hit in the attack and was killed, one local official told the BBC.
The US military and the CIA do not routinely confirm that they have launched drone operations, and Gen Kayani did not specifically name the US or mention drones.
But analysts say only American forces could deploy such aircraft in the region.
The attacks have escalated in the region since US President Barack Obama took office. More than 100 raids were reported in the area last year.