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Ukrainian authorities say well-armed pro-Russian separatists shot down a Malaysia Airlines passenger aircraft with a sophisticated anti-aircraft missile.
The Boeing 777, carrying 280 passengers and 15 crew, crashed near the city of Torez in the Donetsk region about 50km from the Russia-Ukraine border.
Eyewitnesses at the scene say there are no survivors and the crash debris is spread over a large area, which is controlled by pro-Russian separatists.
The codeshare flight with KLM Airlines left Amsterdam around noon local time on Thursday and was due to arrive in Kuala Lumpur this morning.
The crash is another major blow to Malaysia Airlines, with the loss of Flight MH370 somewhere in the Indian Ocean in March.
The latest plane went down while flying at a cruising altitude of about 10,000m (33,000ft) and would require a ground-to-air missile.
Pro-Russian separatists of the self-proclaimed Donetsk People's Republic say they don’t have missiles that go above 3-4000m.
Ukrainian Prime Minister Arseniy Yatsenyuk has ordered a special investigation into the crash, which follows the downing of a Ukrainian AN-26 military cargo aircraft and a Ukrainian SU-25 fighter jet in the same area earlier this week.
Ukrainian authorities say earlier this week they captured a sophisticated Buk (or Beech) Russian anti-aicraft system in this area, much of which is controlled by armed groups backing the Donetsk regime.
Aviation authorities say the crash area has been avoided by civilian aircraft due to conflict between Ukrainian armed forces and the pro-Russian separatists. Most major European airlines say they will no longer fly over this area.
Some reports say Malaysia Airlines Flight MH17 was flying further north than the planned route to avoid bad weather.
In 2001, the Ukrainian military mistakenly shot down a commercial passenger jet that was en route from Tel Aviv to Novosibirsk with a land-to-air missile that was fired during a military exercise.
All the 66 passengers and 12 crew members on board the plane were killed in that crash.