Sen. Thad Cochran William (Thad) Thad CochranEspy wins Mississippi Senate Democratic primary Bottom Line Mike Espy announces Mississippi Senate bid MORE’s (R-Miss.) impending retirement has opened a new path for Tea Party firebrand Chris McDaniel to reach the Senate — a prospect that Majority Leader Mitch McConnell Addison (Mitch) Mitchell McConnellOcasio-Cortez to voters: Tell McConnell 'he is playing with fire' with Ginsburg's seat McConnell locks down key GOP votes in Supreme Court fight Video shows NYC subway station renamed after Ruth Bader Ginsburg MORE (R-Ky.) desperately wants to avoid.

McConnell and other Republican leaders are worried about a reprise of last year’s electoral debacle in Alabama, when another conservative insurgent, Roy Moore Roy Stewart MooreVulnerable Senate Democrat urges unity: 'Not about what side of the aisle we're on' Sessions hits back at Trump days ahead of Alabama Senate runoff Judge allows Roy Moore lawsuit over Sacha Baron Cohen prank to proceed MORE, capitalized on voters’ discontent with the Washington establishment to win the Republican primary, only to lose a Senate seat the GOP was expected to keep.

McConnell favored Mississippi Gov. Phil Bryant (R) appointing himself to fill the vacancy created by Cochran’s retirement, but that hope crumbled Tuesday when Bryant ruled it out.

McConnell is also mulling the prospect of Bryant tapping Lt. Gov. Tate Reeves or Mississippi House Speaker Philip Gunn to replace Cochran, according to GOP sources familiar with internal party discussions.

Mississippi Agriculture Commissioner Cindy Hyde-Smith’s name has also been floated as a possibility.

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But McConnell opposes the ascension of McDaniel, a Tea Party-style conservative who tried to knock off Cochran in 2014 in a brutal, close primary, according to Senate GOP strategists familiar with McConnell’s thinking. McDaniel announced his candidacy against incumbent Sen. Roger Wicker Roger Frederick WickerHillicon Valley: DOJ indicts Chinese, Malaysian hackers accused of targeting over 100 organizations | GOP senators raise concerns over Oracle-TikTok deal | QAnon awareness jumps in new poll Shakespeare Theatre Company goes virtual for 'Will on the Hill...or Won't They?' Republican Senators raise concerns over Oracle-TikTok deal MORE (R-Miss.) last week.

McDaniel, like Moore, has made running against McConnell and the GOP establishment in Washington his central political strategy. McDaniel blasted McConnell and Wicker on Tuesday for “blocking” President Trump Donald John TrumpBiden leads Trump by 36 points nationally among Latinos: poll Trump dismisses climate change role in fires, says Newsom needs to manage forest better Jimmy Kimmel hits Trump for rallies while hosting Emmy Awards MORE’s nominees in the Senate.

“The fact is, Roger Wicker and the Senate Republican leadership are the reason for the delay in getting Trump’s nominees confirmed,” he said in a statement.

When McDaniel announced his challenge to Wicker last week, he accused him of being “too weak to stand up to Mitch McConnell.”

McDaniel is now thinking about running for Cochran’s seat instead of challenging Wicker, but hasn’t made a final decision.

One Senate Republican source warned that McDaniel could split the Republican vote under the unusual special election rules, bolstering the chances that a Democrat could win the Mississippi Senate seat.

“That puts the majority in jeopardy,” the Republican source warned.

Bryant, who has an approval rating above 50 percent, is expected to select Cochran’s replacement within 10 days of the senator’s official retirement on April 1.

That successor will then have to run in a special election in November with a format that does not designate party affiliation on the ballot and allows multiple members of the same party to compete against each other.

If no candidate manages to win majority support, the top two vote-getters will advance to a runoff.

A Republican Party source, however, downplayed the possibility that Republicans could lose the seat, arguing that last year’s special election in Alabama was unique because Moore was accused of sexual misconduct by women when they were teenagers and he was in his 30s.

“There’s not going to be a child predator running in other states,” the source said.

McDaniel is one of at least three Tea Party-style Republican challengers around the country who have tried to gain traction by bashing McConnell and his leadership team, sowing divisions in the Republican electorate.

Former Arizona state Sen. Kelli Ward (R), who is running to replace retiring Sen. Jeff Flake Jeffrey (Jeff) Lane FlakeJeff Flake: Republicans 'should hold the same position' on SCOTUS vacancy as 2016 Republican former Michigan governor says he's voting for Biden Maybe they just don't like cowboys: The president is successful, some just don't like his style MORE (R), has bashed McConnell as a “career insider” who routinely disappoints the conservative base.

Ward has the backing of former White House chief strategist Stephen Bannon, another avowed critic of McConnell’s record, although she distanced herself from Bannon earlier this year.

In Nevada, Danny Tarkanian, a conservative insurgent who is challenging Sen. Dean Heller Dean Arthur HellerOn The Trail: Democrats plan to hammer Trump on Social Security, Medicare Lobbying World Democrats spend big to put Senate in play MORE (R), has also criticized McConnell for not being more ardent in his support for Trump.

Tarkanian blamed the GOP leader’s “Capitol Hill cronies” and “failures to deliver” for last year’s loss of the Alabama Senate seat, which Democrat Doug Jones won.

The Senate Leadership Fund, a super PAC linked to McConnell, spent more than $10 million last year in an attempt to elect then-incumbent Sen. Luther Strange Luther Johnson StrangeSessions hits back at Trump days ahead of Alabama Senate runoff The biggest political upsets of the decade State 'certificate of need' laws need to go MORE (R-Ala.), who was appointed to succeed Jeff Sessions Jefferson (Jeff) Beauregard SessionsGOP set to release controversial Biden report Trump's policies on refugees are as simple as ABCs Ocasio-Cortez, Velázquez call for convention to decide Puerto Rico status MORE when he left to become Trump’s attorney general. But Strange eventually lost the primary to Moore, setting the stage for Moore’s special election loss.

“There’s concern and the concern is focused on three states: Mississippi, Arizona and Nevada,” said a Republican senator who requested anonymity to discuss internal political discussions about the prospects of defending the Senate GOP majority.

The lawmaker added that Joe Arpaio, the former Maricopa County, Ariz., sheriff who became famous for cracking down on illegal immigration, is also a source of concern. Arpaio announced his candidacy for Flake’s seat in January.

The senator warned that what he described as the out-of-the-mainstream views of McDaniel, Ward, Tarkanian and Arpaio could tarnish the GOP’s brand.

Republican lawmakers worry that such anti-establishment conservatives could seize on antipathy toward McConnell in particular and Congress in general to gain political momentum and open the door for Democrats in runoff and general elections.

A second Republican senator warned that McDaniel, who has a history of making controversial political statements, could become an albatross for other Senate candidates in the same way that former Missouri Rep. Todd Akin (R) and former Indiana Treasurer Richard Mourdock were in the 2012 election.

GOP leaders say Akin and Mourdock, who both made damaging remarks about rape and abortion during their bids, fumbled Senate races in Missouri and Indiana that Republicans should have won relatively easily.

McConnell told reporters in October that he would not let history repeat itself by allowing Tea Party challengers who might be less palatable to general election voters win nomination battles.

“We had an experience in 2010 and 2012 nominating candidates in primaries who couldn’t win the general election,” he said.

“Our strategy going forward is to protect our incumbents and to help people get nominated who can actually win elections,” he added.

Democrats, meanwhile, hope that GOP infighting will weaken the party and make it more likely that Senate control flips in November, even as Democrats are faced with defending more vulnerable seats than Republicans.

“Across the Senate map, Republicans are suffering nasty and expensive primaries. These intraparty fights will drain their resources, expose the flaws in all of their candidates and leave their ultimate nominees deeply damaged,” said David Bergstein, press secretary for the Democratic Senatorial Campaign Committee.