Bayh made the decision not to run on Friday, telling a small group of senior staff, but he did not tell President Obama or Reid until today.
His aides say he had been struggling with the decision for the better part of the last year, but Democrats in the Senate seemed to have no clue. Many said his decision caught them completely by surprise, but an adviser to Bayh said it was a deeply personal decision.
Aides say one key difference in the Senate since Bayh's arrival in the U.S. Senate in 1999 is that the center doesn't hold these days. When Bayh arrived in the Senate, he believed he was part of a core of people in the ideological middle who achieved results, said a senior adviser, but the senator believes the split between left and right is much sharper today than it was in 1999.
Even in a bad year for Democrats, Bayh seemed to be in a strong position going into his re-election campaign. His campaign has about $13 million in the bank and he had a double-digit lead in the polls over his most likely opponent, lobbyist and former Republican Senator Dan Coats.
Republicans recently coaxed Coats into running for Bayh's seat, which he held before Bayh was elected in 1998. Coats' candidacy got off to a slow and turbulent start, with questions about his lobbying clients and his residency. But Bayh's exit would make this a much easier race for any Republican.
In order to file for the Republican or Democratic primaries in Indiana, set for May 4, 2010, a candidate needs to deliver a petition containing at least 4,500 signatures including at least 500 signatures form each of the state's nine congressional districts. According to the Indiana Secretary of State's candidate handbook, those petitions can be delivered no later than tomorrow at noon local time.
It appears unlikely that any minor Democratic candidate is likely to have acquired the necessary signatures by tomorrow's deadline, leaving the Democratic primary ballot vacant for U.S. Senate.
One Democratic official said the state party will lean on a provision in state law that allows party leaders to select a candidate on their own in the case of a vacancy on a major-party line. Possible candidates include Democratic Reps. Baron Hill and Brad Ellsworth.
In an interview with ABC News last month, Bayh warned that if Democrats ignored the lessons of the Massachusetts Senate race -- in which Republican Scott Brown emerged as the victor -- it will "lead to even further catastrophe" for the party.
"There's going to be a tendency on the part of our people to be in denial about all this," Bayh said, but "if you lose Massachusetts and that's not a wake-up call, there's no hope of waking up."
In 2008, Bayh was on Barack Obama's short list for vice president, but he emerged as a critical voice in the Democratic party. According to an analysis by Congressional Quarterly, he voted against Obama's position, where clearly stated, more than any other Senate Democrat -- on 23 percent of 79 Senate votes.
ABC News' David Chalian, Jake Tapper and Sunlen Miller contributed to this report.