An Airbus A320 airliner has crashed in the French Alps between Barcelonnette and Digne, French aviation officials and police have said.
The jet belongs to the German airline Germanwings, a subsidiary of Lufthansa.
The plane, flight 4U 9525, had been en route from Barcelona to Dusseldorf with 142 passengers and six crew on board.
French President Francois Hollande said: "The conditions of the accident, which have not yet been clarified, lead us to think there are no survivors."
Mr Hollande said the crash was a tragedy, adding that the area was very difficult to access.
French Alps crash: Live updates
Mr Hollande later called German Chancellor Angela Merkel to express his sympathy, the French presidency said.
The plane issued a distress call at 10:47 (09:47 GMT), the French interior ministry said, although details are unclear.
Search-and-rescue teams are headed to the crash site at Meolans-Revels, said regional council head Eric Ciotti.
Analysis: Nigel Cassidy, BBC's Europe business reporter
Although it began its life as an independent low-cost carrier, Germanwings is wholly owned by its parent Lufthansa.
It operates increasing numbers of the group's point-to-point short-haul routes and takes many passengers from German cities to Mediterranean sunspots.
The airline has an excellent safety record with no previously reported accidents. The average age of its Airbus fleet is just over nine years old, though flight 4U 9525 was a 24-year-old A320.
The plan was to phase out the Germanwings brand and replace it with Eurowings. There has been a longstanding dispute with the Vereinigung Cockpit union over early retirement. Pilots went on strike for three days around this time last year.
French Prime Minister Manuel Valls said he had sent Interior Minister Bernard Cazeneuve to the scene and a ministerial crisis cell had been set up to co-ordinate the incident.
The interior ministry said debris had been located at an altitude of 2,000m (6,500ft).
Interior ministry spokesman Pierre-Henry Brandet told BFM TV that it would be "an extremely long and extremely difficult'' search-and-rescue operation because of the remoteness.
Lufthansa chief executive Carsten Spohr tweeted: "We do not yet know what has happened to flight 4U 9525. My deepest sympathy goes to the families and friends of our passengers and crew.
"If our fears are confirmed, this is a dark day for Lufthansa. We hope to find survivors."
The Airbus A320 is single-aisle passenger jet popular for short- and medium-haul flights.
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