Former Yugoslav President Slobodan Milosevic had been found dead in his cell at The Hague, where he has been on trial for war crimes since 2002.
Milosevic, 64, suffered a heart condition and high blood pressure which had repeatedly interrupted his trial in the Hague on charges of genocide, crimes against humanity and war crimes during the bloody disintegration of Yugoslavia in the 1990s.
Milosevic was sent to The Hague war crimes court in June 2001, eight months after he was toppled in a popular uprising. He was widely blamed in the West for the violent break-up of old socialist Yugoslavia in the 1990s.
"Milosevic was found lifeless on his bed in his cell at the United Nations detention unit," the UN war crimes tribunal said in a statement. "The guard immediately alerted the detention unit officer in command and the medical officer. The latter confirmed that Slobodan Milosevic was dead."
The tribunal said the Dutch police and a Dutch coroner were called in and started an inquiry. A full autopsy and toxicological examination have been ordered. Milosevic's family has been informed, it added.
Milosevic's lawyer Steven Kay ruled out suicide as a cause of death.
"He said to me a few weeks ago, 'I haven't fought this case for as long as I have with any intention to do any harm to myself'," Mr Kay told the BBC.
"He has a history of suicide in his family - both his parents - but as far as he was concerned, his attitude to me was quite the opposite from that. He was determined to keep fighting his case."
"He was in poor health, he had a recognised heart condition, a cardiovascular problem," Mr Kay said. "In the last six months he also developed pains inside his head which was linked to a problem with his ears."
France described Milosevic as "the main architect of the Balkan wars and ethnic cleansing that killed tens of thousands of people."
French foreign minister Philippe Douste-Blazy told reporters at an EU summit:
"With the death of Milosevic, one of the main actors if not the the main actor in the Balkan wars of the late 20th century."
"I would like to spare a thought for all those who suffered so much from ethnic cleansing, tens of thousands of men, women and children, which Milosevic conceived and planned."
Serbia-Montenegro Foreign Minister Vuk Draskovic said it was a pity Milosevic had not been tried in his own country.
"Milosevic organised many many assassinations of people of my party, of people of my family... He ordered a few times asasination attempts against my life," Mr Draskovic said.