A win by Republican Scott Brown on Tuesday would eliminate Democrats' 60-seat supermajority in the Senate and imperil some of Obama's key legislative objectives, including an overhaul of health care - a longtime cause of Kennedy's.
The swift rise of Brown, a relatively low-profile Republican state senator, in his race against Democratic state Attorney General Martha Coakley has spooked Democrats who had considered the seat one of their most reliable.
Kennedy, who died in August, held the post for 47 years. The last time Massachusetts elected a Republican to the U.S. Senate was 1972.
Massachusetts has a liberal reputation, but a full half of voters here are registered independent. Despite his conservative record, Brown has been tapping in to that independent streak, reports CBS News correspondent Nancy Cordes.
Brown has tried to turn Democrats' expectation of an easy win to his advantage, proclaiming, "It's not the Kennedy seat, it's the people's seat."
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On Monday, Brown made another bus tour of the state, shaking hands with Boston Bruins fans at lunchtime and ending his day in his hometown of Wrentham, Mass., before an enthusiastic crowd of supporters, again touting the endorsement of former Red Sox pitcher Curt Schilling.
"It's us against the machine," he told the group, urging them to vote. "Make sure that we send a message to Washington that business as usual is not how we like to do business."
Coakley also toured the state, enlisting the aid of top Democrats and making a final pitch to female voters. If she wins, Coakley would be the first woman elected to the Senate from Massachusetts.
With the stakes so high, Obama rolled out a last-minute television ad and the campaign launched automated phone calls from Vice President Joe Biden and Kennedy's widow, Vicki Kennedy, targeting voters who supported Obama in 2008. Members of the state's all-Democratic congressional delegation, including Sen. John Kerry and Rep. Barney Frank, also campaigned for Coakley.
"Every vote matters, every voice matters," Obama said in the ad. "We need you on Tuesday."
Both campaigns enlisted small armies of volunteers to staff phone banks and trudge through a mix of heavy snow and slush to remind their voters to get to the polls.
It's unclear whether the full-court press by unnerved Democrats was enough to blunt the surging Brown.
A Suffolk University survey taken Saturday and Sunday showed Brown with double-digit leads in three communities the poll identified as bellwethers: Gardner, Fitchburg and Peabody. But internal statewide polls for both sides showed a dead heat.
For Brown's staunchest supporters, such as Glen Stump, 47, a software engineer from Andover, Democrats' appeals fell on deaf ears.
"I hope he can stop this Obamacare legislation," Stump said, using critics' nickname for the health care overhaul bill. "I think it's being run in a completely partisan manner."
A third candidate, Joseph L. Kennedy, a Libertarian running as an independent, said he's been bombarded with e-mails from Brown supporters urging him to drop out and endorse the Republican. Kennedy, who was polling in the single digits and is no relation to the late senator, said he's staying in.