At least 19 people have died as violent protests erupted on the streets of Pakistan's main cities in anger at an anti-Islam film made in the US.
Fourteen people were killed in the port city of Karachi and a further five died in the north-western city of Peshawar, hospital officials said.
Protesters clashed with police outside the diplomatic enclave in the capital, Islamabad, near the US embassy.
There has been widespread unrest over the amateur film, Innocence of Muslims.
Dozens of people have been reported wounded and BBC correspondents said some were in a critical condition.
Protests have already left several people dead around the world, including Pakistan, where the government had appealed in advance for peaceful protests, declaring a holiday and "day of love" for the Prophet Muhammad.
Although US targets have borne the brunt of protests against the film, anti-Western sentiment has been stoked further by caricatures of the Prophet Muhammad published this week in the satirical French magazine, Charlie Hebdo.
France shut embassies and other missions in around 20 countries across the Muslim world on Friday.
Protests were banned in France itself and in Tunisia, where France is the former colonial power, but there were widespread demonstrations elsewhere.
- A peaceful protest took place outside the US embassy in the Malaysian capital, Kuala Lumpur
- Some 3,000 people marched in the southern Iraqi city of Basra
- Thousands burned US and French flags in the Bangladeshi capital, Dhaka
- Crowds rallied in Baalbek in Lebanon in a protest organised by the Shia militant group, Hezbollah, burning US and Israeli flags
- Thousands of Libyans joined a march in Benghazi against Islamist militia who have been blamed for an attack in which the US ambassador and three other American officials were killed
But it was in Pakistan's major cities that protesters took to the streets in big numbers and tried to march on US diplomatic buildings.
US Secretary of State Hillary Clinton said that "all governments have the duty, the solemn duty, to defend diplomatic missions", AFP news agency reported.
The worst of the violence took place in the country's biggest city, Karachi, and the north-western city of Peshawar, close to Pakistan's lawless tribal belt.
Police in Karachi fired live bullets in the air to disperse crowds after a large rally that had begun peacefully turned violent. Several cinemas and banks were set on fire and there were reports of looting.
When police tried to stop the protesters heading to the US consulate, there were reports of gunfire from the crowd and a policeman was killed.
Health officials said the bodies of dead protesters were taken to two hospitals.
In Peshawar, protesters ransacked cinemas and a driver for Pakistan's ARY TV was killed when police opened fire on the crowd.
In the capital, Islamabad, which saw its first clashes between protesters and security forces on Thursday, a police checkpoint was burnt as demonstrators tried to breach the "red zone" where the main embassies and government offices are based.
Police used live rounds and tear gas as the crowd swelled to thousands of people.
The BBC's Aleem Maqbool said the focal point of people's anger was the US embassy and he had seen more people injured in one hour than all of Thursday.
In Lahore, protesters toppled over shipping containers that police had placed on the road to block access to the US consulate.
The low-budget film that has prompted the unrest was made in the US and is said to insult the Prophet Muhammad.
Its exact origins are unclear and the alleged producer for the trailer of the film, Nakoula Basseley Nakoula, is in hiding.
Anti-US sentiment grew after a trailer for the film dubbed into Arabic was released on YouTube earlier this month.
US citizens have been urged not to travel to Pakistan and the US embassy has paid for adverts on Pakistani TV showing President Barack Obama and Secretary of State Hillary Clinton condemning the film.
Mobile phone services had been suspended in many of the biggest cities to limit the potential for violence but critics questioned the Pakistani government's decision to declare a public holiday.
Government security adviser Rehman Malik told the BBC that the public holiday was the right decision and the protests would have gone ahead regardless.
"Imagine if I had not done the holiday, school would open, shops would open, the transport was on the road. Who could have handled it?" he said.