Air France told CNN the jet was making the 11-hour flight from Rio de Janeiro to Charles de Gaulle airport in Paris when contact was lost.
Brazil's air force launched a search near the archipelago of Fernando de Noronha in the Atlantic Ocean, 365 km (226 miles) from Brazil's coast, the country's state media said.
Air France said flight AF447 was carrying 216 passengers in addition to a crew of 12. The plane is listed as an Airbus A330.
The airline said it "shared the emotion and the concern of the families concerned" adding that friends and relatives waiting at the airport would be taken to a special area.
A crisis center is being set up at Charles de Gaulle where the plane had been due to land at 11.15 a.m. local time.
"We are very worried," an aviation official told Agence France-Presse. "The plane disappeared from the screens several hours ago. It could be a transponder problem, but this kind of fault is very rare and the plane did not land when expected."
The Airbus 330 is a twin-engine long-range aircraft introduced into commercial aviation in the 1990s.
Transport analyst Kieran Daly told CNN that the lack of communication with the aircraft "does suggest it was something serious and catastrophic."
He said the aircraft involved is believed to be one delivered to Air France in April 2005. 
Watch aviation expert
describe possible scenarios ยป
"It is an extremely young fleet by aviation standards," he said. "The A330 is state of the art with extremely reliable engines made by General Electric."
CNN air travel expert Richard Quest says the plane, a stalwart of trans-Atlantic routes, has an impeccable safety record.
"It has very good range, and is extremely popular with airlines because of its versatility," he said.
