France's junior transport minister said there were "no survivors" from the crash of the Germanwings Airbus A320, a low-cost subsidiary of Lufthansa, in a remote part of the Alps that is extremely difficult to access.
Civil aviation authorities said they lost contact with the plane, which was carrying 144 passengers and six crew, and declared it was in distress at 10:30 am (1500 IST).
"The distress signal showed the plane was at 5,000 feet in an abnormal situation," said Alain Vidalies, minister of state for transport.
French President Francois Hollande said the plane crashed in an area very difficult to access and rescuers would not be able to reach the site for several hours.
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"I want to express all our solidarity to the families affected by this tragedy," Hollande told reporters.
The plane was travelling from the Spanish coastal city of Barcelona to the German city of Duesseldorf when it went down in the ski resort area of Barcelonnette.
A French police helicopter dispatched to the site of the crash reported spotting debris in a mountain range known as "Les Trois Eveches," which reaches 1,400 metres in altitude.
The government said "major rescue efforts" had been mobilised, but accessing the remote region would present severe challenges.
"The zone is snow-bound and inaccessible to vehicles, but could be overflown by helicopters," said Vidalies.
The plane belonged to Germanwings, a low-cost affiliate of German airline Lufthansa based in Cologne which until now had no record of fatal accidents.
"We are suspending our planned strike as a result of the emotions created in the control rooms by the crash, particularly in Aix-en-Provence," the union's spokesman Roger Rousseau told AFP.