They said tests conducted after the seizure showed a tumor in Kennedy's left parietal lobe. Preliminary results from a biopsy of the brain identified the cause of the seizure as a malignant glioma, they said.
His treatment will be decided after more tests but the usual course includes combinations of radiation and chemotherapy.
Kennedy has been hospitalized in Boston since Saturday, when he was airlifted from Cape Cod after a seizure at his home.
"He has had no further seizures, remains in good overall condition, and is up and walking around the hospital," said the statement by Dr. Lee Schwamm, vice chairman of the Department of Neurology at Massachusetts General Hospital and Dr. Larry Ronan, Kennedy's primary care physician.
They said Kennedy will remain in the hospital "for the next couple of days according to routine protocol."
Kennedy's wife and children have been with him each day since he was hospitalized. Senator Kennedy's son, Rep. Patrick Kennedy, D-R.I., plans to stay at the hospital for the time being.
"Obviously it's tough news for any son to hear," said spokeswoman Robin Costello. "He's comforted by the fact that his dad is such a fighter, and if anyone can get through something as challenging as this, it would be his father. So he's optimistic, he's hopeful, but obviously he's concerned."
President Bush was notified by his staff of Kennedy's diagnosis at 1:20 p.m.
"He said he was deeply saddened and would keep Senator Kennedy in his prayers," spokeswoman Dana Perino said.
Malignant gliomas are a type of brain cancer diagnosed in about 9,000 Americans a year -- and the most common type among adults. It's an initial diagnosis: How well patients fare depends on what specific tumor type is determined by further testing.
Average survival can range from less than a year for very advanced and aggressive types -- such as glioblastomas -- or to about five years for different types that are slower growing.
News of the diagnosis hit hard for colleagues on both sides of the aisle.
"I'm really sad," former Sen. Bob Kerrey, D-Neb., said when told in a Senate hallway about Kennedy's condition. "He's the one politician who brings tears to my eyes when he speaks."
"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.