After his unexpected retirement in 2010 from the Senate, Mr. Bayh joined a Washington law and lobbying firm, McGuireWoods. Republicans have tried to paint him as a handmaiden of special interests, a charge he predictably rejects. “I’ve missed public service since the day I retired from the Senate,” Mr. Bayh said.

Indiana has a recent history of punishing once-popular politicians who they think have “gone Washington.” Former Senator Richard G. Lugar, one of the state’s most respected political figures, was ousted in a primary in 2012 by a Tea Party challenger.

But Senator Dan Coats, a Republican whose retirement created the opening for Mr. Bayh, made a comeback in 2010 after his own revolving-door turn as a lobbyist. Mr. Coats noted that the climate this year seemed more hostile. “It might matter more this year than ever,” he said.

Others have found themselves going from beloved to spurned. Former Senator Bob Kerrey had been gone from Nebraska for nearly 20 years when he tried to return to the Senate in 2012, leaving his wife and child back in New York City as he faced bruising attacks.

“By November, half the people thought I had never lived in Nebraska,” said Mr. Kerrey, who was defeated and returned to New York as quickly as he had left. “Republicans are better than Democrats are in doing that sort of thing. They did such a good job they probably saved my marriage.”

But Mr. Bayh enjoys many advantages that keep him as the front-runner in the race, Democrats and Republicans agree. The son of former Senator Birch Bayh, Mr. Bayh is part of a Midwestern political dynasty that spans generations of voters. A moderate who was long viewed as working well with Republicans, Mr. Bayh fits the state’s self-image as almost defiantly sensible.