Unidentified gunmen firing on an anti-government rally in the Yemeni capital Sanaa have killed at least 45 people and injured 270, doctors told the BBC.
The gunmen fired from rooftops overlooking the central square in what the opposition called a massacre.
President Ali Abdullah Saleh declared a national state of emergency but denied his forces were behind the shooting.
US President Barack Obama has condemned the violence, urging Mr Saleh to allow peaceful protests.
In a statement, he said those responsible for Friday's violence "must be held accountable".
Separately, France demanded an end to attacks "by security forces and armed pro-government groups... against people exercising their rights to free speech and demonstration", Reuters reports.
Yassin Noman, rotating president of Yemen's umbrella opposition group, was quoted by Reuters news agency as saying there was "no longer any possibility of mutual understanding" between the protesters and President Saleh, and he should resign.
Another opposition spokesman, Mohammad al-Sabri, accused Mr Saleh of presiding over a "massacre".
"This is part of a criminal plan to kill off the protesters, and the president and his relatives are responsible for the bloodshed in Yemen today," he told the Associated Press news agency.
Soon after the shooting in the capital, the country's Tourism Minister, Nabil al-Faqih, resigned in protest.
A month of violence has gripped Yemen and demonstrators reportedly gathered in other cities across the country on Friday:
Row of bodies
The BBC's Abdullah Ghorab in Sanaa says the level of anger over the casualties is unprecedented among Yemenis.
The declaration of an emergency is being seen by some as an attempt to find legal cover for suppressing peaceful protests and blocking media coverage, our correspondent adds.
Photographs from Sanaa showed bloodstained people being carried through crowds.
Other photos showed a row of dead bodies, with injuries which appeared to be consistent with bullet wounds, laid out in a mosque.
Doctors at a field hospital set up in the square, which protesters have named Taghyir (Arabic for "change") Square, issued an urgent call for blood, ambulances and medical supplies.
According to a statement from the field hospital, a total of 617 people were injured on Friday, 270 with gunshot wounds and 347 "poisoned by gas". Tear gas was fired by security forces during the day.
Abdul Malek Al-Yussefi, a doctor in the field hospital, told the BBC that what had happened in the square was a "crime in all possible terms".
"There was live ammo fired," he said.
"Many of the wounded are in critical condition. The injuries are mostly in the head and chest but there are also injuries all over the body. We have cases targeted randomly and others were clearly shot to be killed. Most of those killed were shot in the head and chest."
Announcing the state of emergency, President Saleh said the country's national defence council had decided to impose a curfew on "armed men in all cities".
"Security forces and armed forces will take responsibilities to maintain public security," he added.
Yemen is one of a number of countries in the region that have seen unrest since the presidents of Egypt and Tunisia were ousted in popular revolts.
Thousands of people have turned out for regular demonstrations in cities including Sanaa, Aden, Taez, calling for corruption and unemployment to be tackled and demanding the president step down.
Some 40% of the population live on $2 (£1.20) a day or less in the country, and a third face food shortages.
The protests have often been met by riot police or supporters of President Saleh armed with knives and batons.
The president has been in power for 32 years, facing a separatist movement in the south, a branch of al-Qaeda, and a periodic conflict with Shia tribes in the north.
He has said he will not seek another term in office in 2013 but has vowed to defend his regime "with every drop of blood".