Israeli troops have fired on pro-Palestinian protesters in the Israeli-occupied Golan Heights, with Syrian state TV saying 20 are dead.
The protesters marched towards a border fence to denounce the Israeli occupation of Arab land.
The march was held on the anniversary of the 1967 War, when Israel seized the Golan Heights, the West Bank and Gaza.
Israel had vowed to prevent a repeat of a similar march last month, in which hundreds of people breached the fence.
The US state department said it was "troubled" by the "loss of life".
"We call for all sides to exercise restraint," it said. "Provocative actions like this should be avoided."
Several hundred demonstrators - Palestinians and their Syrian supporters - marched to the razor-wired fencing and trenches close to the frontier village of Majdal Shams at around noon.
Many carried Palestinian flags and threw rocks and rubbish over the fence.
Israel's military said its soldiers shouted warnings in Arabic and fired warning shots in the air, before aiming at the legs of those who had reached the fence.
After live gunfire failed to disperse the crowds, Israeli troops fired volleys of tear gas over the border. Many people fled while others lay on the ground.
Syrian TV said more than 300 protesters had been wounded.
An Israeli military spokeswoman told The Jerusalem Post newspaper they were only aware of 12 injuries.
Israeli government spokesman Mark Regev told the BBC that the Syrian figures could not be trusted.
Ahead of Sunday's march, Israeli Prime Minister Benjamin Netanyahu said he would not allow "extremists" to breach Israel's borders.
"I have instructed our security forces to act with determination and restraint in order to protect our sovereignty our borders," he said at the weekly cabinet meeting in Jerusalem.
Another Israeli military spokeswoman, Avital Leibovich, told reporters: "This is an attempt by the Syrian regime to divert the world's attention from the Syrian bloodshed that has been taking place in recent weeks."
She added that Israeli forces were better able to stop border protests now than they were last month as they had since prepared "for a variety of operation scenarios".
Israel seized the Golan Heights from Syria in the closing stages of the 1967 war, along with other territories including the West Bank, Gaza and East Jerusalem. The anniversary is known in Arabic as the Naksa, or "setback".
On 15 May, tens of thousands of pro-Palestinian demonstrators marched on the borders with Israel, in the Palestinian territories, Syria, Jordan and Lebanon.
They were marking the 63rd anniversary of Nakba, which in Arabic means "catastrophe" - when hundreds of thousands of Palestinians lost their homes amid the fighting after the creation of the state of Israel in 1948.
At least 12 people died during the 15 May demonstrations, which at one point saw hundreds manage to cross into the Golan Heights.