A US airstrike in Pakistan targeted al Qaeda's second-in-command, Ayman al-Zawahri, but he was not injured, according to senior Pakistani military sources.
The attack killed at least 18 villagers - eight women, five men and five children.
Pakistan condemned the airstrike and regretted the loss of civilian lives, Information Minister Sheikh Rashid Ahmed said, adding "we will not allow such an incident to reoccur".
"According to preliminary investigations there was foreign presence in the area and that in all probability was targeted from across the border in Afghanistan," the Foreign Ministry said in a statement. "The investigations are still continuing.
"Meanwhile the Foreign Office has lodged a protest with the US Ambassador in Islamabad," the ministry said.
CNN quoted sources saying the CIA ordered last night's strike after receiving intelligence Zawahri was in the village of Damadola near the border with Afghanistan.
ABC News quoted Pakistani military sources as saying five of those killed were "high-level" al-Qaeda figures.
Shah Zaman, who lost his three children in a pre-dawn US air strike on his village, walks through the rubble of his house this morning
CIA-operated unmanned drones were believed to have been used in the attack on Damadola village, across the border from Kunar province in eastern Afghanistan, the US sources said.
A high-ranking Pakistani official said Zawahri, the deputy of al-Qaeda leader Osama bin Laden, was not in the village, although he was believed to have made visits to the Bajaur area in the past.
The United States has offered a reward of $25 million for Zawahri or bin Laden.
The strike was reportedly ordered based on information Zawahri and Taliban leader Mullah Mohammad Omar had been invited to a dinner to celebrate this week's Muslim Eid al-Adha festival.
Another intelligence official said four US aircraft had fired four missiles that destroyed three houses in the attack on the village in the Bajaur tribal agency opposite Afghanistan's insurgent-troubled Kunar province.
A military spokesman at US Central Command in Florida said there had been no official report of an attack in Pakistan. US sources in Washington said it would not be known whether Zawahri was killed until the remains of the dead were examined.
People from Damadola said no foreigners, only local people, were present and were killed in yesterday's attack. "I know all the 18 people killed. There was neither al Zawahri nor any other Arab among them. Rather they were all poor people of the area," Haroon Rashid, the area's National Assembly representative, was quoted as saying by the Afghan Islamic Press news agency.
The incident came days after Pakistan, an important ally in the US-led war on terrorism, lodged a strong protest with US-led forces in Afghanistan, saying cross-border firing in the nearby Waziristan area last weekend killed eight people.
On the run since US-led forces toppled Afghanistan's Taliban government in, bin Laden and Zawahri are believed to have been hiding in the rugged border areas under the protection of Pashtun tribes.
Analysts say several high profile arrests in Pakistan and elsewhere mean bin Laden's and Zawahri's network has lost much of its capability to launch attacks. But while they have been partly overshadowed by al-Qaeda's leader in Iraq, Abu Musab al-Zarqawi, they are still regarded with awe among Islamist militants and their sympathisers. In a video aired last week, Zawahri hailed "Islam's victory in Iraq" and said the United States was being defeated there.