An Airbus A320 with 142 passengers and 6 crew members has crashed in Digne region, southern France.
French President Francois Hollande said he believed none of those on board had survived.
"There were 148 people on board," Hollande said. "The conditions of the accident, which have not yet been clarified, lead us to think there are no survivors."
French media said there were 142 passengers and six crew on board.
Hollande said there was likely to be a significant number of Germans on the flight from Barcelona to Duesseldorf.
He added: "The accident happened in a zone that is particularly hard to access."
A spokesman for France's DGAC aviation authority said the airliner crashed near the town of Barcelonnette about 100 km (65 miles) north of the French Riviera city of Nice.
French accident investigators were heading for the crash site in Meolans-Revel, a remote and sparsely inhabited commune in the foothills of the French Alps.
Airbus said it was aware of reports about the crash.
"We are aware of the media reports," Airbus said on Twitter. "All efforts are now going towards assessing the situation. We will provide further information as soon as available."
Officials at Barcelona airport said the flight took off at 0855 GMT (0455 ET).
The crashed A320 is 24 years old and has been with the parent Lufthansa group since 1991, according to online database airfleets.net