Jackson, Miss. — Longtime Republican Sen. Thad Cochran, of Mississippi, said on Monday he will resign because of health problems — triggering what could be a chaotic special election to fill the seat he has held for a generation.

Cochran, who turned 80 in December and has been in poor health, has been a sporadic presence on Capitol Hill in recent months. He stayed home for a month last fall, returning to Washington in October to give Republicans the majority they needed to pass a budget plan. He has since kept a low profile and an aide ever present at his side.

“I regret my health has become an ongoing challenge,” Cochran said in a statement. “It has been a great honor to serve the people of Mississippi and our country. I’ve done my best to make decisions in the best interests of our nation, and my beloved state. … My hope is by making this announcement now, a smooth transition can be ensured so their voice will continue to be heard in Washington, D.C.”

Cochran said his resignation is effective April 1, allowing Republican Gov. Phil Bryant to appoint a temporary replacement to fill the seat until a special election Nov. 6. The winner would serve until the end of Cochran’s term in January 2021.

Cochran’s departure sets off a scramble within a state Republican Party already struggling to manage a disaffected conservative faction. The special election is expected to attract several candidates, including the outspoken, tea party-backed state senator who came close to defeating Cochran in a bitter 2014 Republican primary. Republican Chris McDaniel, who said last week he would challenge Mississippi’s other GOP senator, Roger Wicker, said on Monday it is “premature” to say whether he will run for the newly open seat.

“I want him to be healthy and happy,” McDaniel said of Cochran. “We disagree politically, but I have nothing but respect for his service.”

Republicans in Washington are hoping to prevent a rough and costly primary season as they struggle to defend their narrow 51-49 hold on the Senate. Some Republicans have doubts about McDaniel’s ability to win a general election. And after Republicans’ bruising loss in Alabama last year, party leaders are eager to block any risky candidates.

Mike Espy, a Democrat who served as President Bill Clinton’s secretary of agriculture, said Monday he has a “strong intention” to run for Cochran’s seat. In 1986, Espy became the first African-American in modern times to win a congressional seat in Mississippi.

Cochran was first elected to the Senate in 1978 after serving six years in the House.

A mild-mannered Southerner, Cochran came to the Senate when it had a far clubbier atmosphere and he played an insider’s game throughout his seven terms — particularly as a member of the powerful Appropriations panel, which had long been a bipartisan powerhouse and way to funnel taxpayer dollars back home.

Cochran chaired the committee twice and used the post to channel money to Mississippi and other Gulf Coast states for Hurricane Katrina recovery after the 2005 storm.