Pakistan on Friday summoned the US ambassador and lodged a strong protest over a drone strike in a tribal region which killed 35 people, the foreign ministry said.
US ambassador Cameron Munter was told "that such strikes were not only unacceptable but also constituted a flagrant violation of humanitarian norms and law," the ministry said in a statement.
Pakistan's civilian and military leaders have already strongly condemned on Thursday's drone strike against a militant hideout in North Waziristan tribal region and demanded an apology and explanation from the US.
Civilians and police were among those killed when US missiles ploughed into a militant training compound in Datta Khel town, 40 kilometres (25 miles) west of Miranshah, the main town in tribal North Waziristan.
The ministry said that Munter was met by foreign secretary Salman Bashir who conveyed "a strong protest" regarding on Thursday's attack by a CIA-operated pilotless drone.
"It was evident that the fundamentals of our relations need to be revisited. Pakistan should not be taken for granted nor treated as a client state," the statement said.
"It was for the White House and the state department to hold back those who have been trying to veer Pakistan-US relationship away from the track."
The ministry said Pakistan would not attend a meeting in Brussels with officials from the Washington and Kabul on security in Afghanistan, scheduled for March 26.
Ambassador Munter said that he understood clearly that this was not a "pro forma demarche" (a formality) and that he would rush to Washington to convey Pakistan's message to the highest levels of the US administration, the ministry said.