Sen. Barbara Mikulski (D) of Maryland is retiring after five terms in office, according to numerous news reports. The longest-serving female senator in US history been a legislative force in her home state and the nation for a generation, from her political beginnings as a neighborhood activist who helped block a highway through Baltimore’s Fells Point neighborhood, to her service as the first woman to chair the powerful Senate Appropriations Committee.

In stepping down, she’ll create a huge political opening in a state where top-level positions are generally stable. Who will run for her seat? That’s a question that’s zooming around Maryland’s political world even before the lights have dimmed at her retirement press conference.

Will Martin O’Malley run? The former governor is setting up for a White House bid, but his chances are slim to slimmer against the Hillary Clinton machine. It’s possible he could opt for the Senate instead and a little national seasoning before trying again in a later presidential year.

But he’d be no lock for the Democratic Senate nomination, much less the general election. That leads some observers to opine that it’s more likely than not he sticks with his current plans. Losing an intra-mural bid for a Senate nomination might kill off Mr. O’Malley’s national ambitions in a stroke.

The state has many other strong possible Democratic candidates who have been waiting for this chance, and they won’t step aside just because somebody senior to them in party ranks wants the seat.

There’s Rep. Chris Van Hollen, for instance, the congressman from prosperous Montgomery County along Washington, D.C.’s northern edge. There’s Rep. Donna Edwards, who represents Prince George’s County to D.C.’s east. There’s even Maryland Comptroller Peter Franchot, who made a bid for the gubernatorial nomination in 2014 and has long been an active and ambitious force in the state Democratic Party.

“Lots of O’Malley buzz, but the likely contenders for the seat are Van Hollen & Donna Edwards. Both on Senate track,” tweets Josh Kraushaar, National Journal politics editor, this morning.

Could the seat swing Republican? That’s another big question in the wake of the Republican Party’s 2014 gains, which included the governorship of Maryland. New Gov. Larry Hogan is the face of what local members of the GOP hope will be their resurgence in a state that’s long been considered deep blue.

That’s possible but unlikely. Governor Hogan benefited from a convergence of factors: He was a good candidate; his opponent, Lt. Gov. Anthony Brown, was a middling candidate who seemed to believe the seat was in the bag; and 2014 was a midterm election, meaning many Democrats stayed home because President Obama wasn’t on the ticket.

But 2016 is a presidential election, and turnout rises in presidential years. The percentage of the state electorate composed of Democrats will almost certainly rise, since it’s low-income and minority Democrats who typically don’t go to the polls in off-years.

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Kyle Kondik, a University of Virginia political scientist and editor of the Crystal Ball political tip sheet, thinks a Republican senator from Maryland is unlikely.

“Should be a swarm of MD Ds falling over each other to replace Mikulski. State prolly too D at prez level for Rs to compete. Safe D,” he tweeted this morning.