The Obama administration said Tuesday that there had been a "marked and troubling" increase in civilian casualties in Syria since Russia began airstrikes in September.
Human rights groups report hundreds of civilians have been killed by Russian missile strikes on emergency medical workers, hospitals, schools and markets.
State Department spokesman Mark Toner said Secretary of State John Kerry brought up the matter in a telephone call with Russian Foreign Minister Sergei Lavrov.
"We've consistently urged all sides of the conflict to take all feasible precautions to reduce the risk of harming civilians and comply with their obligations under international humanitarian law," Toner said.
Russia has denied causing civilian deaths in Syria. It says its airstrikes against what it calls "terrorists" are carefully coordinated with the Syrian army to avoid all civilian targets.
Russia has said its mission in Syria is directed against Islamic State. The U.S. says Russia has been targeting the moderate opposition and is trying to prop up President Bashar al-Assad's floundering government.
Toner also said the killing of a top Syrian rebel leader last week complicated efforts for a cease-fire.
An airstrike fired either by Russia or Syrian forces killed Zahran Alloush, the head of an opposition group called Jaysh al-Islam. The group fought against Islamic State while backing a political settlement.
Toner called such killings "counterproductive."
"When we see these kinds of actions taken against their leadership ... it is our hope that it does not send a discouraging message to other members of the Syrian opposition who have gone to Riyadh, who have expressed a willingness to take part in this process," he said.
The United Nations is looking to convene international talks on Syria on January 25.
The U.N. brokered two rounds of peace negotiations between the Syrian government and rebels early last year, but those talks broke apart with little progress.