Several members of the state's all-Democratic congressional delegation would also be expected to jump into a Kennedy-less field. They include Rep. Mike Capuano, a liberal from Somerville, Mass., and Rep. Stephen Lynch, a conservative Democrat from South Boston.
Rep. Niki Tsongas, the widow of the late Sen. Paul Tsongas, D-Mass., might also consider a run. But with only two years' service in the House, some in the state believe she may instead choose to stay in the House.
University of Massachusetts-Lowell chancellor Marty Meehan, who left Congress two years ago but still has nearly $5 million in his federal campaign account, also will mull a run. But those close to Meehan say he's likely to conclude that he'd be better off staying in his current job longer. He would be pressed to take a leave of absence, if not resign his post, to campaign for the Senate.
Another intriguing possibility would be for Patrick to run for Senate, perhaps in lieu of a re-election bid in 2010. The governor is a close friend of President Barack Obama's, although his political standing has eroded in his home state after a series of early blunders.
Political insiders believe that the two longest-serving -- and highest-profile -- House members from the state, Reps. Barney Frank and Ed Markey, are unlikely to run for Senate. Both Democrats were likely candidates if Kerry's seat had come open in 2004, but both have ascended to powerful chairmanships under Democratic control of Congress, and would hesitate before sacrificing their seniority.
The race will be difficult for any Republican candidate to break through, although a big-name or self-funded candidate could change the dynamics.
Romney -- who lost a close race to Kennedy for the Senate seat in 1994 -- may face calls from national voices to run. But with his sights trained on the presidency, he is unlikely to risk his political standing by jumping in the race.
Former Gov. Paul Cellucci and former White House chief of staff Andy Card also are mentioned as possible candidates. But their ties to former President George W. Bush likely would become major campaign issues.
Kerry Healey, who was Romney's lieutenant governor and lost a 2006 gubernatorial race, is considered by GOP insiders to be a likely candidate and, perhaps, the party's best shot at picking up the seat.
Other possible Republican candidates include state Sen. Scott Brown; Christopher Egan, a real estate developer and the son of EMC Corp. founder Jack Egan; and former U.S. Rep. Peter Torkildsen.
If Patrick is empowered to make an interim selection, possible candidates include former Gov. Michael Dukakis, the Democrats' 1988 presidential nominee.
"We passed health reform in the Dukakis administration 20 years ago here," said Johnston, the Kennedy family friend who served in Dukakis' cabinet, "and wouldn't it be a wonderful thing if his was the deciding vote on behalf of Sen. Kennedy?"