Nato air strikes targeted the centre of Muammar Gaddafi's seat of power early on Monday, destroying a multi-storey library and office and badly damaging a reception hall for visiting dignitaries.
Gaddafi's whereabouts at the time of the attack on his sprawling Bab al-Azizya compound were unclear. A security official at the scene said four people were hurt.
The strike came after Gaddafi's forces unleashed a barrage of shells and rockets at the besieged rebel city of Misrata, in an especially bloody weekend that left at least 32 dead and dozens wounded.
The battle for Misrata, which has claimed hundreds of lives in the past two months, has become the focal point of Libya's armed rebellion against Gaddafi since fighting elsewhere is deadlocked.
Video of Misrata civilians being killed and wounded by Gaddafi's heavy weapons, including Grad rockets and tank shells, have spurred calls for more forceful international intervention to stop the bloodshed in the rebel-held city.
In Brussels, a Nato spokesman said the alliance is increasingly targeting facilities linked to Gaddafi's regime with government advances stalled on the battlefield.
"We have moved on to those command and control facilities that are used to co-ordinate such attacks by regime forces," the spokesman said of the strike on Bab al-Azizya.
Gaddafi's son, Saif al-Islam Gaddafi, struck a tone of defiance. He claimed that Gaddafi has "millions of Libyans with him" and said Nato's mission was doomed to fail.
"In history, no country has achieved victory with spies and traitors and collaborators. Nato, you are the losers," he said.
At least two missiles struck Bab al-Azizya early on Monday, and the booms could be heard several miles away.