"The incident occurred near Charikot, Nepal while the aircraft was conducting humanitarian assistance and disaster relief operations," said Major Dave Eastburn, spokesman for US Pacific Command.
The UH-1Y Huey had just dropped off supplies and was headed to another destination, officials said.
Before the chopper went missing, there was "some chatter about a fuel problem" on the radio from the helicopter crew, Pentagon spokesman Colonel Steven Warren said.
A search by US aircraft before nightfall had not spotted any sign of smoke or any crash site, raising hopes the helicopter may have made a safe emergency landing, he said.
The Nepalese army was conducting a search on the ground but no aircraft could fly until daylight to look for the crew.
There was so far no beacon signal detected from the helicopter crew, officials said.
The chopper was carrying six US Marines and two soldiers from the Nepalese army, officials said.
About 300 US military troops have deployed to support the relief effort in Nepal, where aftershocks continue to claim lives after last month's massive quake.
Relief teams from around the world are still working to provide water, food and medical assistance to Nepalis after the April 25 quake.
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