BOSTON — Even as prayers in Massachusetts and around the country are going out for Senator Kennedy, whom doctors diagnosed yesterday with a malignant brain tumor, the news is prompting quiet consideration of a political environment devoid of America’s second-longest-serving senator.

RELATED: Kennedy Returns to Cape Cod To Sail and Recuperate.

Given the seriousness of Mr. Kennedy’s condition and the recognition of his formidable will, few in the Bay State are eager to talk publicly about what his illness might mean politically. Even so, the announcement underlines the idea that Mr. Kennedy, first elected in 1962 to fill his brother’s seat, might someday exit the stage.

The news of the senator’s diagnosis, which pre-empted programming on local broadcast outlets yesterday and dominated cable news coverage throughout the afternoon, threatens to upset the existing political order in the state.

The last prospect of an open Senate seat in Massachusetts came in 2004, when it looked briefly as if Senator Kerry might win the presidency. At that time, the leading prospective candidates included a quintet of congressmen from the Greater Boston area — Barney Frank, Edward Markey, Martin Meehan, Michael Capuano, and Stephen Lynch. Mr. Frank has since become the chairman of the House Financial Services Committee and Mr. Markey the head of the telecommunications and Internet subcommittee.

Should Mr. Kennedy leave his position, state law, passed during the 2004 election cycle to prevent the then governor, Mitt Romney, from appointing a potential replacement for Mr. Kerry, calls for a special election. Messrs. Capuano and Lynch, both of whom represent parts of Boston, would make formidable candidates. Other potential Democratic candidates could include current state office holders — Governor Patrick; the treasurer, Timothy Cahill; and the attorney general, Martha Coakley — as well as Mr. Kennedy’s nephew Joseph Kennedy, a former state attorney general, Scott Harshbarger, and even Mr. Kennedy’s wife, Victoria Reggie Kennedy [A slideshow of potential Democratic successors to Mr. Kennedy is included above].

On the Republican side, preliminary speculation has centered on Mr. Romney, who challenged Mr. Kennedy for Senate in 1994, and the president of Harvard Pilgrim Health Care, Charles Baker.

“Don’t bet against Ted Kennedy being around for another five years, but nonetheless it puts the Massachusetts political community on notice,” a Democratic political analyst and supporter of Mr. Kennedy’s, Louis DiNatale, said. “This just kicks open everything. Does Patrick run for the U.S. Senate seat? It literally does open up a plethora of opportunities for a half a dozen major figures.”

For many, the announcement prompted a call for Mr. Kennedy’s recovery. “People’s first feeling will be to say a quiet prayer,” a former lieutenant governor whose father replaced John F. Kennedy in the House and served with Senator Kennedy in the state delegation as speaker of the House, Thomas O’Neill, said. “Americans and folks in Massachusetts ought to be saying a quiet vigil.”

Still, the episode is presenting for some an opportunity to take the long view on the senator’s achievements.

Other than a two-year interregnum between 1960 and 1962, a son of Joseph P. Kennedy has held the Senate seat since 1952. Edward Kennedy’s service in the Senate has spanned multiple eras: He joined less than a year after John Glenn made the first manned space flight, and he placed his stamp on this year’s contentious Democratic presidential primary when he endorsed Senator Obama over Senator Clinton. For a time the most reliable Republican talking point and fund-raising argument, Mr. Kennedy has nonetheless worked as a partner over the years with such figures as Senator Hatch, Senator McCain, and President Bush.

Mr. Kennedy was the driving force behind a series of legislative achievements that have over time become the bipartisan consensus: He sponsored the Americans with Disabilities Act, increased funding for the National Institutes of Health, and created government-backed student loans.

“He was the most important, most effective lawmaker of the 20th century. I don’t think there was another person who affected the lives of so many,” the author of “Edward M. Kennedy: A Biography,” Adam Clymer, said. “Over a long career, he has accomplished more than any other lawmaker in the 20th century.”

“If you were to put 99 senators in a room together and ask them to write down the name of the three most powerful, substantive people in the Senate and then write the name of the most popular senator, his is the only name that would appear on both lists,” a Democratic political consultant, Michael Goldman, said.

A former Washington bureau chief of the Boston Globe, Martin Nolan, said he remembered meeting Mr. Kennedy when he announced his intention to run for the Senate in 1962. “Little did any of us know then that he would become the George Washington of the Senate, one of its legendary giants, not only in seniority — third all time, behind Robert Byrd and Strom Thurmond — but in accomplishment,” Mr. Nolan said.