EgyptAir flight MS804from Paris to Cairo has disappeared from radar, the airline says.
The Egyptian airline says there are 56 passengers, seven crew members and three security personnel on board.
The plane was flying at 37,000ft when it went missing over the eastern Mediterranean. An official said the plane lost contact with radar at 02:45 Cairo time.
EgyptAir says search and rescue teams have been deployed.
The passengers on board included 30 Egyptians, 15 French citizens, one Briton, as well as people from Belgium, Algeria, Sudan, Chad and Portugal, EgyptAir says.
EgyptAir says the Airbus A320 disappeared about 10 miles into Egyptian air space and the relevant authorities have been notified.
Amid fears that the plane has crashed into the Mediterranean Sea, the Greek authorities have joined Egyptian armed forces in the search operation.
Flight MS804 left Paris’ Charles de Gaulle airport at 23:09 local time on May 18 and was scheduled to arrive in Cairo soon after 03:00 local time on May 19.
An airport official, quoted by Egypt’s state-run newspaper al-Ahram, said the last contact with the plane had been 10 minutes before it disappeared – and no distress signal had been sent.
Egyptian PM Sherif Ismail has arrived at the airport in Cairo, along with the families of those on board, state-run Nile News TV reports.
In October 2015, a Russian passenger plane flying from Sharm el-Sheikh crashed over the Sinai peninsula killing all 224 people on board. Officials in Moscow and Egypt later said the aircraft was brought down by an explosive device. ISIS militants said they had bombed the plane.