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“I’m leaving the Senate now, but I’m not leaving the fight,” he said. “I’ve decided to join the Heritage Foundation at a time when the conservative movement needs strong leadership in the battle of ideas. No organization is better equipped to lead this fight.”

Mr. DeMint told CNN that he thinks there is “no question” he will have a greater impact on the conservative movement running the Heritage Foundation — a powerhouse conservative think tank that dominates Republican policy circles — than by staying in the Senate.

He also told the cable network that if Republican presidential candidate Mitt Romney had won the election last month, he “would have thought differently about” stepping down.

Heritage isn’t shy about targeting Republicans it considers lacking conservative bona fides, a philosophy Mr. DeMint will uphold. When conservative radio host Rush Limbaugh jokingly asked the senator whether House Speaker John A. Boehner, Ohio Republican, forced him out of office, Mr. DeMint laughed and said; “It might work a little bit the other way.”

Mr. DeMint said he never intended for the Senate to be a career for him. He served six years in the House and won election to the Senate in 2004 and re-election in 2010.

His seat is safe for Republicans, with the GOP firmly in control of South Carolina’s political landscape and Gov. Nikki R. Haley, a Republican, able to pick his immediate successor.

Mrs. Haley’s appointment for Mr. DeMint’s replacement will serve until the state’s next general election in 2014. And with no clear-cut candidate, just who she picks is anyone’s guess.

A popular choice to replace Mr. DeMint is Rep. Tim Scott, who was elected to his second term last month and will be the only black Republican in Congress when the new Congress convenes in January.

Others mentioned as possible replacements include South Carolina GOP Reps. Mick Mulvaney and Trey Gowdy, state Treasurer Curtis Loftis, state Sen. Tom Davis and former state Attorney General Henry McMaster.

Mr. DeMint’s departure means that both South Carolina Senate seats will be on the ballot in 2014. The move is seen as a break for Mr. Graham’s re-election efforts, as potential conservative Republican and Democratic challenges likely will run for the open seat.

“This takes a lot of pressure off Sen. Graham,” Mr. Huffmon said.

Mr. Graham brushed off questions regarding how Mr. DeMint’s Senate exit will affect is re-election campaign, saying “I have no idea how this affects me politically.”

Mr. Paul praised Mr. DeMint for blazing a trail that made it easier for himself and other “constitutional conservatives” to find a place in Congress.

“Because of Sen. DeMint’s tireless efforts there now is a significant voice for liberty in the U.S. Senate,” Mr. Paul said.

Mr. Rubio credited Mr. DeMint as being “one of the main reasons why I’m in the U.S. Senate.”

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