A Boeing 777 flying from Amsterdam to Kuala Lumpur comes down in Ukraine after reportedly being hit by a ground-to-air missile.
The Malaysia Airlines plane, which was flying from Amsterdam to Kuala Lumpur, was travelling at an altitude of 33,000 feet (10,000 metres) when it was shot down, Russia's Interfax reported.
An adviser to the Ukrainian interior ministry told the news agency the Boeing 777 was brought down by a Buk ground-to-air missile.
All 280 passengers and 15 crew members who were on the plane are believed to have died, he added.
A spokesman for Malaysia Airlines, still reeling from the loss of flight MH370 in March, confirmed it had lost contact with flight MH17, which took off from Amsterdam's Schiphol airport at 12.15pm local time.
The flight disappeared from radar as it flew over Ukrainian airspace, the spokesman said.
A number of videos apparently filmed near the village of Grabovo, Donetsk, where the plane came down, showed plumes of thick, black smoke rising high into the air.
TV channel Russia 24 broadcast similar pictures, while a correspondent for the Reuters news agency at the scene said he could see the wreckage of a burning aircraft and bodies on the ground.
The plane, which one eyewitness said split in two on impact, is almost unrecognisable in pictures of the crash site, with debris scattered across a vast area.
Alexander Borodai, the eastern Ukraine separatist leader, said the aircraft was shot down by Ukrainian government forces - a claim backed by a separatist from Krasnyi Luch, who told Reuters the rebels did not have weapons capable of shooting down a plane at such height.
However, officials in Kiev denied any involvement, with Ukrainian Prime Minister Arseniy Yatsenyuk ordering an immediate investigation into what he described as a "catastrophe".
The Kremlin said Russian President Vladimir Putin had offered "his sincerest words of sympathy and support to families and friends of the victims", while Malaysian Prime Minister Najib Razak said he was "shocked" by the tragedy.
Data from Flightradar24 indicates the plane had just passed the city of Kremenchuk, around 300km (186 miles) from the Russian border, when it disappeared.
Aviation expert Major Charles Hayman told Sky News: "It's highly likely this aircraft was flying along a fault line between Russian and Ukrainian defences.
"It's possible the Ukrainians flapped a bit, thought it was hostile and shot it down.
"It looks like someone failed to recognise this was a civilian plane."
A spokesman for Boeing said its "thoughts and prayers" are with the families and loved ones of those on board the plane, adding it "stands ready to provide whatever assistance is requested by authorities".
Relatives of the victims of the MH370 tragedy also released a statement, saying: "Who would do such poisonous thing to a civil aeroplane?
"Passengers on board are ordinary people, just like our relatives. Why let them experience the torture? Why let other people feel the same pain as we do?"