Maryland Sen. Barbara Mikulski, the longest serving woman in the history of Congress, announced her retirement Monday.
The 78-year-old Democrat was up for a sixth term next year.
Her retirement is expected to result in a competitive Democratic primary battle in the blue state with Maryland Reps. Donna Edwards, Chris Van Hollen, Elijah Cummings and John Delaney mentioned a possible candidates. Former Maryland Democratic Gov. Martin O'Malley's name also has been mentioned.
Mikulski became the longest-serving woman in Congress in 2012. She was elected to the House in 1976 and has served in the Senate since 1987.
"This was a very big decision," Mikulski said in announcing her retirement in the Baltimore City waterfront neighborhood of Fell's Point, near where she was born.
Mikulski said she couldn't point to a specific moment as the highlight of her 39-year Capitol Hill career. But she cited her work helping special-needs children and getting funding for fire departments. And she said she was proud that she was able to get her "best ideas" from everyday people, then take their messages to Washington.
"Do I spend my time raising money, or do I spend my time raising hell," Mikulski said of her remaining 22 months in office.
Mikulski becomes the second major Democratic female senator to announce a retirement this election cycle.
California Sen. Barbara Boxer said in January that she would not seek a fifth term.
Mikulski also is the highest-ranking Democrat on the Senate Appropriations Committee.
There was speculation in 2010 that Mikulski would not seek a fifth term after she broke her ankle in fall 2009 and had to use a wheelchair for several months.
“Barbara is a force of nature on the Senate floor and she will be missed both by her colleagues and her constituents," said Montana Sen. John Tester, chairman of the Democratic Senatorial Campaign Committee. "I am confident that in November 2016 we will elect a new Democratic senator who will fight for Maryland every day."
Maryland has not had a Republican in the Senate since 1987 when Sen. Charles Mathias retired but last year elected a GOP governor, Larry Hogan, in a upset victory.
“After winning the governor’s race ... there's no question that an open Senate seat in Maryland instantly becomes a top pickup opportunity for Republicans," said National Republican Senatorial Committee spokeswoman Andrea Bozek. "While Democrats get ready for a bloody primary, we will have a top recruit waiting for whoever emerges."
Fox News’ Chad Pergram, Kara Rowland and Joseph Weber and The Associated Press contributed to this report.