It was the second U.S. air strike in three months against IS in Libya, where the hardline Islamist militants have exploited years of chaos following Muammar Gaddafi's 2011 overthrow to build up a presence on the southern shores of the Mediterranean Sea.
The Pentagon said it had targeted an IS training camp and killed a Tunisian militant linked to major attacks on tourists in Tunisia.
Among those Washington said it targeted was Noureddine Chouchane, a Tunisian blamed by his native country for attacks last year on a Tunis museum and the Sousse beach resort, which killed dozens of tourists.
"Destruction of the camp and Chouchane's removal will eliminate an experienced facilitator and is expected to have an immediate impact on ISIL's ability to facilitate its activities in Libya, including recruiting new ISIL members, establishing bases in Libya, and potentially planning external attacks on US interests in the region," the Pentagon said, using an acronym for IS, also known as ISIS or Daesh.
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The mayor of the Libyan city of Sabratha, Hussein al-Thwadi, told Reuters the planes hit a building in the city's Qasr Talil district, home to many foreigners.
He said 43 people had been killed and six wounded. The death toll could not immediately be confirmed with other officials.
The White House said it could not yet confirm the results of the air assault, but that it was committed to fighting IS.
"It's an indication that the president will not hesitate to take these kinds of forceful, decisive actions," White House
spokesman Josh Earnest said. Other U.S. officials said they believed it is highly likely Chouchane is dead.
In Libya, photos released by the municipal authorities showed a massive crater in grey earth. Several wounded men lay bandaged in hospital.
The strikes targeted a house in a residential district west of the centre, the municipal authorities said in a statement.
The house had been rented to foreigners including Tunisians suspected of belonging to IS and medium-calibre weapons including machineguns and rocket-propelled grenades had been found in the rubble, the statement said.
Tunisian security sources have said they believe Tunisian IS fighters have been trained in camps near Sabratha, which is close to the Tunisian border.
The carnage (AAP) Source: AAP
The air strikes came just days after a warning by President Barack Obama that Washington intended to "take actions where we've got a clear operation and a clear target in mind".
"And we are working with our coalition partners to make sure that as we see opportunities to prevent ISIS from digging in, in Libya, we take them," Obama said on Tuesday.
Britain said it had authorised the use of its airbases to launch the attack.
"I welcome this strike that has taken out a Daesh training camp being used to train terrorists to carry out attacks,"
Defence Secretary Michael Fallon said in a statement.
IS runs a self-styled caliphate across swathes of Iraq and Syria, where it has faced air strikes from a US-led coalition since 2014.
Thwadi, the Sabratha mayor, said some Tunisians, a Jordanian and two women were among the dead, and several Tunisians who had recently arrived in Sabratha were among survivors. He gave no further details.
Deeper in chaos
Since Gaddafi was overthrown five years ago by rebel forces backed by NATO air strikes, Libya has slipped deeper into chaos, with two rival governments each backed by competing factions of former rebel brigades.
A U.N.-backed government of national accord is trying to win support, but is still awaiting parliamentary approval. It is opposed by factional hardliners and has yet to establish itself in the capital Tripoli.
IS has expanded, attacking oil ports and taking over Gaddafi's home city of Sirte, now the militant group's most important stronghold outside its main redoubts in Syria and Iraq.
Calls have increased for a swift Western response to stop the group establishing itself more permanently and using Libya as a base for attacks on neighbours Tunisia and Egypt.
The leading Democrat in the US House of Representatives' Intelligence Committee, Rep. Adam Schiff, urged a better US plan for North Africa.
"Ultimately, we need a comprehensive North African strategy in which we, our allies and our regional partners conduct operations to deny ISIS a sanctuary where it can continue to organize and train, establish an alternate base to Syria and Iraq, and threaten the fragile democracy of Tunisia," he said in a statement.
Western officials and diplomats have said air strikes and special forces operations are possible as well as an Italian-led "security stabilisation" plan of training and advising.
US and European officials have in the past insisted Libyans must first form a united government and ask for help, but they also say they may still carry out unilateral action if needed.
The US estimates that the number of militants directly affiliated with IS or sympathetic to it now operating in Libya is in the "low thousands," or less than 5,000, a US government source said.
Last November the United States carried out an air strike on the Libyan town of Derna, close to the Egyptian border, to kill Abu Nabil, an Iraqi commander in IS.
Last June, a US air strike targeted veteran Algerian militant Mokhtar Belmokhtar and other jihadists meeting in eastern Libya. His fate is unclear.
The United Nations warned on Friday that efforts to confront IS must be done in accordance with international law.
"The fight against Daesh in Libya should be Libyan-led. It is therefore critical that the Libyans seize the opportunity to unite under a government of national accord," UN spokesman Stephane Dujarric told reporters.
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