President Donald Trump took a swing at Sen. Susan Collins late Thursday night, calling on Republicans to vote “the exact opposite” of Maine’s senior senator, who is up for reelection next year.

“Republicans, when in doubt, vote the exact opposite of Senator Susan Collins,” Trump said in a social media post at 10 p.m. Thursday. “Generally speaking, you can’t go wrong. Thank you for your attention to this matter and, MAKE AMERICA GREAT AGAIN!”

Collins defended her voting record in a written statement to the Press Herald on Friday.

“I cast each vote based on what is right for Maine and America,” she said. “Sometimes that means I agree with the president and sometimes I disagree.”

Collins, the top Senate appropriator, has voted against Trump’s two top priorities — his so-called “One Big Beautiful Bill” that extended tax breaks for the wealthy while cutting Medicaid, and a $9 billion rescission package that reduced foreign aid and federal funding for public broadcasting. Both passed without her support.

Despite those votes, along with votes against some of Trump’s controversial Cabinet nominees, the president has refrained from criticizing Collins by name. She is the only Republican from New England in Congress and the only senator facing reelection in a state that voted for former Vice President Kamala Harris, a Democrat, in 2024.

Trump’s social media post may mark an end to the detente with Collins, who has a complicated relationship with the president. He was never her top choice for president and she also voted to impeach Trump after the Jan. 6, 2021, riots at the Capitol Building. Further public attacks against Collins could complicate her reelection chances.

Mark Brewer, chair of the political science department at the University of Maine, said it’s too soon to say whether Trump’s post is a warning shot, or marks the beginning of a campaign against Collins.

“Sometimes Trump’s late-night social media posts are just venting one-offs,” Brewer said. “Sometimes they are part of a long-running pattern of criticism and attack. And sometimes they mark the start of something new and different. We’ll need to wait and see into which of these categories, if any, this message from Trump falls.”

The criticism also comes as Collins, who this year achieved her longtime goal of leading the appropriations committee, has sought to maintain the historically bipartisan Senate appropriations process, despite calls from Trump’s top budget official, Russell Vought, to make the budgeting process more partisan.

Collins voted to confirm Vought as budget director, despite his views that the president can withhold funding appropriated by Congress for projects that don’t align with Trump’s agenda, a view Collins and Democrats say violates federal law and infringes on Congress’ constitutional power of the purse.

It also comes as reporters in Washington, D.C., have reported that the White House is ruminating about finding a more MAGA-aligned Republican to run in Maine.

Collins, 72, has not yet formally announced her candidacy for a sixth term, but she has repeatedly said she intends to seek reelection.

She is potentially facing two primary opponents, although only one appears to be actively campaigning.

Carmen Calabrese, a Kennebunkport businessman who moved to Maine five years ago from Tallahassee, Florida, is running as a Trump ally and has repeatedly called out Collins for opposing the president’s priorities, calling her “an obstructionist.”

No big-name Democrats have stepped into the race.

Bristol resident Jordan Wood, who grew up in Lewiston and was a former chief of staff for U.S. Rep. Katie Porter, D-Calif., is mounting the most aggressive challenge, while Brunswick resident David Costello, who unsuccessfully challenged U.S. Sen. Angus King last year, is also running.

National Democrats, meanwhile, are hoping that Gov. Janet Mills, who is termed out of office and gained national notoriety after standing up to Trump in front of other governors at the White House in February, will challenge Collins, but she has been noncommittal, neither expressing interest or ruling out a run.

Phillip Rench, a former SpaceX engineer, is running as an independent.