"I am so deeply saddened I have lost the words," Sen. John Warner, R-Va., said in a Senate hallway. Warner said he and Kennedy had been friends for 40 years. Both served on the Senate Armed Services Committee together.

Kennedy, the second-longest serving member of the Senate and a dominant figure in national Democratic Party politics, was elected in 1962, filling out the term won by his brother, John F. Kennedy.

His eldest brother, Joseph, was killed in a World War II airplane crash. President Kennedy was assassinated in 1963 and his brother Robert was assassinated in 1968.

Kennedy is active for his age, maintaining an aggressive schedule on Capitol Hill and across Massachusetts. He has made several campaign appearances for Sen. Barack Obama in February, and most recently last month.

Kennedy, the senior senator from Massachusetts and the Senate's second-longest serving member, was re-elected in 2006 and is not up for election again until 2012.

Were he to resign or die in office, state law requires a special election for the seat no sooner than 145 days and no later than 160 days after the vacancy occurs.

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AP reporter Lauran Neergaard in Washington contributed to this report.