Tara Air said rescue helicopters had been deployed to search for the Twin Otter aircraft, which lost contact with air traffic control eight minutes after it left the western town of Pokhara on Wednesday morning.
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"A plane that took off from Pokhara for Jomsom this morning is out of contact," Tara Air spokesman Bhim Raj Rai told AFP.
"There are 18 passengers, including two foreigners, and three crew members, on board."
Jomson is a popular trekking destination in the Himalayas about 20 minutes' flight from Pokhara, which lies 225 kilometres west of Kathmandu.
Nepal, which is still reeling from a devastating earthquake last April, has suffered a number of air disasters in recent years, dealing a blow to its tourist industry.
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Most have been attributed to inexperienced pilots, poor management and inadequate maintenance.
The country's aviation sector has come under fire from international authorities and in 2013 the European Union banned all Nepalese airlines from flying there.
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