Americans James Rothman and Randy Schekman and German-born Thomas Sudhof have been awarded the Nobel Medicine Prize for their groundbreaking work on how the cell organises its transport system.
The trio, who all work at US universities, were honoured for "their discoveries of machinery regulating vesicle traffic, a major transport system in our cells", the Nobel committee said in its announcement in Stockholm, Sweden, on Monday.
Their research has helped explain processes as varied as the release of insulin into the blood, communication between nerve cells and the way viruses infect cells.
Schekman said he was awakened at 1am at his home in California by the chairman of the prize committee and was still suffering from jetlag after returning from a trip to Germany the night before.
"I wasn't thinking too straight. I didn't have anything elegant to say," he told The Associated Press. "All I could say was `Oh my God,' and that was that."
He called the prize a wonderful acknowledgment of the work he and his students had done and said he knew it would change his life.
"I called my lab manager and I told him to go buy a couple bottles of Champagne and expect to have a celebration with my lab," he said.
Rothman and Schekman received the Albert Lasker Basic Medical Research Award for their discoveries in 2002 - an award often seen as a precursor of a Nobel Prize.
The announcements of Nobel laureates will continue this week and next with physics, chemistry, literature and peace.
Each prize is worth $1.2m.
Established by Swedish industrialist Alfred Nobel, the Nobel Prizes have been handed out by award committees in Stockholm and Oslo since 1901. The winners always receive their awards on December 10, the anniversary of Nobel's death in 1896.
Last year's medicine award went to Britain's John Gurdon and Japan's Shinya Yamanaka for their contributions to stem cell science.