Beijing - United States Senator Edward M Kennedy who was diagnosed with a malignant brain tumor in May 2008 died on Wednesday.
Senator Kennedy, who was affectionately known as "Teddy", 77, was the longest serving Senator. He became a member of the Senate in 1962 to replace his brother when he resigned to become president, and was re-elected seven times.
He has been an active supporter of President Barack Obama. The Kennedy family announced his death in a brief statement in the early hours of Wednesday.
"Edward M. Kennedy, the husband, father, grandfather, brother and uncle we loved so deeply, died late Tuesday night at home in Hyannis Port (Massachusetts)," the Kennedy family said in a statement.
Mr Kennedy was the only one of four brothers to die a natural death.
His brother Joseph was killed in an air crash in World War II, and both President John F Kennedy and presidential hopeful Robert F Kennedy were assassinated.
There have already been a number of tributes made to the former senator. Former First Lady Nancy Reagan says she is "terribly saddened; Ronnie (Ronald Reagan) and Ted could always find common ground and they had great respect."
Senator Kennedy's cancer diagnosis and then his death have stirred speculation over who might succeed the third-longest serving US senator, and whether a new generation could emerge from under his shadow.
Many younger Kennedys are active in civic life but none on the scale of Ted Kennedy.
Options are limited for another Kennedy to inherit the Senate seat held by the family for nearly five decades. Kennedy's nephew, Joseph, - the eldest son of Robert Kennedy - is often cited as a possibility.
He served six terms as a US congressman from Massachusetts and now runs the nonprofit Citizens Energy Corp, which delivers cheap heating oil to the state's poor.
Other Kennedy torch-bearers include Ted Kennedy's son, 42-year-old Representative Patrick Kennedy, a Democratic congressman from neighboring Rhode Island. He would need to move to Massachusetts if he were to run for his father's seat.
