Senator Edward Kennedy, the last senior member of the political dynasty which played a dominant role in the United States for almost a century, has died at the age of 77.
In a statement, the Kennedy family announced he had died on Tuesday night at his home in Hyannis Port in Massachusetts.
The Democratic senator was diagnosed with a malignant brain tumour in May last year and his failing health meant he could not attend the funeral of his sister Eunice Kennedy Shriver earlier in August.
Edward Moore Kennedy was born in the Boston suburb of Brookline on 22 February 1932, the youngest of nine children of Joseph P Kennedy and his wife Rose Fitzgerald Kennedy, the BBC reports.
Ted or Teddy Kennedy, as he was affectionately known, took the helm of one America's most fabled political families after his brothers John F Kennedy and Robert Kennedy were assassinated in 1963 and 1968, respectively.
Ted Kennedy became a member of the Senate in 1962 to replace John F Kennedy when he resigned to become president, and was re-elected seven times. He was an active supporter of current president Barack Obama.
Senator Kennedy was one of the most influential and longest-serving politicians in American history and was known as a consummate congressional dealmaker, championing issues including healthcare and education.
But his own presidential aspirations were badly damaged when he was given a suspended sentence for leaving the scene of a fatal accident on the Massachusetts island of Chappaquiddick in 1969.
At his death, he was the third longest serving senator in American history, behind Robert C Byrd and Storm Thurmond, according to the US Senate website.