At least 17 people have been killed in a suspected US drone strike on a compound in north-west Pakistan, Pakistani officials say.
At least two missiles were fired at a house in North Waziristan tribal region early on Wednesday, the deadliest drone attack in Pakistan this year.
It is the third such attack since new PM Nawaz Sharif won elections in May. He has demanded an end to such attacks.
A government statement said the strike violated Pakistan's sovereignty.
"Pakistan has repeatedly emphasised the importance of bringing an immediate end to drone strikes," a foreign ministry spokesman said.
"They are counter-productive, entail loss of innocent civilian lives and have human rights and humanitarian implications."
In a separate development, at least six security personnel are reported to have been killed and at least six more injured in an early morning attack by militants at a checkpoint near Peshawar.
At least two more are reported to be missing, possibly kidnapped by the attackers.
Reports citing local officials said most of those killed in the drone strike were thought to be from the militant Haqqani group.
Officials say four missiles were fired by a US drone, targeting two houses and two vehicles, near Miranshah, the main town in North Waziristan. A number of other people were also injured.
The Haqqani network has been described by US military commanders as one of the most resilient militant groups operating in Afghanistan.
The troubled border region is a known stronghold for al-Qaeda and Taliban militants.
Seven people were killed in a similar strike on 8 June, also in North Waziristan, just three days after the new prime minister was sworn in.
After that incident the Pakistani government summoned a senior US diplomat in protest, condemning what it called a "violation of Pakistan's sovereignty and territorial integrity".
At least two key leaders of the Pakistani Taliban have been killed in earlier US drone strikes this year. Mullah Nazir was killed in January and Waliur Rehman was killed in May, shortly after Mr Sharif swept to election victory.
The BBC's Richard Galpin in Islamabad says that the latest air strike by US forces will further heighten tensions between Washington and the new Pakistani government.
Mr Sharif has called for a joint strategy to stop US drone strikes. The issue is hugely controversial in Pakistan, where parts of the government and military have often been accused of criticising the use of drones in public, but co-operating in private.
Drone strikes are a source of severe tension between the US and Pakistan.
It is estimated that between 2004 and 2013, CIA drone attacks in Pakistan killed up to 3,460 people.
About 890 of them were civilians and the vast majority of strikes were carried out by the Obama administration, research by the Bureau of Investigative Journalism said.
Earlier this year, Mr Obama called the strikes part of a legitimate campaign against terrorism, but he also pledged more programme transparency and stricter targeting rules.