The move dealt an immediate blow to Republicans hoping to take control of the Senate in November and gave Democrats new hope of winning the longtime GOP-held seat.
"As I have long said, what motivates me is producing results for those who have entrusted me to be their voice and their champion, and I am filled with that same sense of responsibility today as I was on my first day in the Maine House of Representatives," Snowe said in a statement. "I do find it frustrating, however, that an atmosphere of polarization and 'my way or the highway' ideologies has become pervasive in campaigns and in our governing institutions."
The news came as a surprise to officials in both national parties. Snowe, 65, is in good health and for months had been laying the groundwork for a strong re-election effort, putting together a campaign team, keeping a busy schedule of events in the state and raising campaign money. She had more than $3.3 million in her campaign account at the end of last year, her last campaign finance report showed.
She spent more than a year working to beat back a tea party challenge, shifting her positions to the right in some cases and spending considerable time allaying the concerns of conservatives in Maine.
Snowe earned a reputation as an independent voice in her 33 years in Congress, but was frustrated by the sharp partisanship and gridlock that has come to characterize the upper chamber recently. She was the only Republican who voted for a version of President Barack Obama's health care overhaul, joining Democrats and casting a vote for the plan in the Senate Finance Committee. She came under intense criticism from conservatives, even after she voted with the GOP to oppose the final legislation.
Snowe epitomized the Northeast centrist Republican, a rare breed in a Senate increasingly dominated by Southern Republicans.
"She comes from a line of moderate Republicans from John Chafee to John Heinz that made really working across the aisle a virtue," said Sen. John Kerry, D-Mass. "It's been really sad to see that virtue derided in so many Republican primaries the last couple years."
Obama said her career shows what can be done when both parties work together.
"From her unwavering support for our troops, to her efforts to reform Wall Street, to fighting for Maine's small businesses, Senator Snowe's career demonstrates how much can be accomplished when leaders from both parties come together to do the right thing for the American people" Obama said.
Republican Sen. Scott Brown of Massachusetts called Snowe a voice of reason in the Senate.
"We all are going to miss her independence and her ability to build bridges on some of the toughest issues," he said.
Snowe's fellow Republican senator and centrist, Susan Collins of Maine, said she was surprised and devastated by the announcement.
"Nobody can replace Olympia in the Senate," she said. "It's going to be a real void."
The Maine Democratic Party was also caught off guard. Snowe's exit from the race could boost Democrats who are facing tough odds this election cycle. Senate Democrats hold a 51-47 majority with two independents who caucus with them.
"This is a total game changer. It elevates this race to a top-tier race in the nation," said Ben Grant, the state Democratic Party chairman. "Obviously, this is going to cause a great deal of turmoil in the Maine political scene."
Already there were four Democrats running for Snowe's seat, including former Secretary of State Matthew Dunlap and state Rep. John Hinck. But the sudden vacancy means Democrats in both Maine and Washington may look for a stronger challenger.
Candidates have only until March 15 to collect the 2,000 signatures necessary to qualify for the November ballot. Maine Democratic officials Tuesday night planned to speak privately with the state's two Democratic members of Congress, Reps. Mike Michaud and Chellie Pingree. Neither had previously expressed interest in challenging Snowe, but the vacancy changes everything. Michaud issued a statement saying he was "seriously considering" a run.
Despite a disastrous 2010 election in which Republicans won both chambers of the Maine Legislature as well as the governorship, Democrats have traditionally done well at the statewide level in Maine. State voters have not supported a Republican in a presidential contest since 1988.
Snowe was facing her first primary fight this year after cruising to a third term in 2006 with 74 percent of the vote, and was viewed by some as vulnerable because of her moderate position at a time when the tea party was gaining influence in Maine. But she had a healthy war chest and remained popular.
Snowe said she was confident she would have won re-election, but saw a "vital need for the political center in order for our democracy to flourish and to find solutions that unite rather than divide us." She said she sees opportunities to build support for that change from outside the Senate, though she did not elaborate.
"To this day, I remain deeply passionate about public service, and I cherish the opportunity I have been given for nearly four decades to help improve the lives of my fellow Mainers," she said.
Last week, one of her GOP challengers dropped out of the primary, choosing to run as an independent, leaving Scott D'Amboise as the only other GOP candidate in the race, but other Republicans could decide to enter now.
Snowe's decision makes her the third Maine senator in the past two decades to voluntarily relinquish a seat to which they could have won re-election. Democratic Sen. George Mitchell Mitchell chose not to run in 1994 and Republican Sen. William Cohen did likewise in 1996.
Snowe is married to former Maine Gov. John McKernan. She was widowed at 26 when her first husband, state Rep. Peter Snowe, died in a car crash. She won a 1973 election to fill his vacant seat. Five years later, she was elected to the U.S. House where she served for 16 years before winning her Senate seat.
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Associated Press Writers Steve Peoples, Donna Cassata and Andrew Miga in Washington, Clarke Canfield in Portland and Steve LeBlanc in Boston contributed to this report.
