It's also, ironically, a "pickup opportunity" for Democrats – a contest that could help them retake control of the House in November.
It was Ryan who solidified the former swing district into firm GOP territory and his exit changes that.
“There’s no natural heir apparent,” said a Wisconsin GOP strategist about Ryan's 1st Congressional District.
“We’re going to have to fight to keep,” said the strategist of the seat. “It should be ours but we’re can’t take it for granted.”
“The only way it doesn’t get to a big primary is if Reince decides to run,” the strategist said.
June 1st is the GOP filing deadline, giving possible candidates about eight weeks to decide.
But, in addition to Priebus, there are a lot of names being bandied about by Republicans in the know.
One is state House Speaker Robin Vos, who is also the former district director for Rep. Mark Neumann, who used to hold the first district.
Another is Bryan Steil, who sits on the University of Wisconsin System Board of Regents and is general counsel at Charter NEX Films. He’s from a prominent Janesville family.
State Sen. David Craig is a former congressional aide to Ryan. He ran his Kenosha district office for nine years.
Also being mentioned is state Rep. Tyler August, who is a speaker pro tem, and state Reps. Samantha Kerkman and Amy Loudenbeck.
None of them responded to ABC’s request for comment. The primary is August 14.
“Wisconsin Republicans are committed to keeping this Congressional seat and I am confident that our eventual nominee will uphold Paul Ryan’s legacy of principled, conservative leadership,” said Brad Courtney, chairman of the Wisconsin Republican Party, in a statement.
Ryan will not endorse a candidate, said Kevin Seifert, the executive director of Team Ryan.
“Though he has no plans to endorse in the GOP primary, Speaker Ryan is committed to making sure that a Republican represents Wisconsin’s 1st Congressional District in the House of Representatives come November," Seifert said in a statement.
“There are many qualified conservatives who would be effective representatives for Wisconsin’s 1st Congressional District, and Paul Nehlen isn’t one of them. His bigoted rhetoric and his reprehensible statements should disqualify him from holding any public office and we are confident voters in Southern Wisconsin feel the same way," Seifert said.
Ryan cited his loyalty to the district in his decision not to run. He noted the “normal politician thing” is to run and then retire after the election but his conscience “could not handle going out that way.”
Randy Bryce, an ironworker and Army veteran, raised $2.1 million in the first quarter of 2018 and is part of the party’s “Red to Blue” program, which is designed to give candidates who met certain criteria extra resources in their contests.
"Paul Ryan decided to quit today rather than face Randy Bryce and the voters,” Bryce said in a statement. “With nearly $5 million raised to date, a strong field program aided by organized labor, a broad coalition of support locally and nationally, Randy Bryce is incredibly well positioned to be the next Representative for the First District. Electorates far more conservative than Wisconsin's First have already elected Democrats in special elections in Wisconsin and across the country."
He has to get through a primary of his own. Cathy Myers, an Army veteran and Janesville School Board member, is also running.
President Donald Trump won the district by 10 points in 2016 but President Barack Obama won it in 2008.
Ryan has held the seat since 1999 and has served as speaker since 2015. He was previously the chairman of the House Ways and Means Committee and the House Budget Committee.
He won reelection in 2016 by 35 points.