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EUGENE, Ore. — An unrestrained Donald Trump called Hillary Clinton an “unbelievably nasty, mean enabler” who “destroyed” the lives of her husband’s mistresses during a rally in Oregon on Friday night.

The comments, made during an evening rally in Eugene, Ore., marked the sharpest tone he’s taken against the Democratic frontrunner since becoming his party’s presumptive nominee, and the first time he’s been so direct in referencing Bill Clinton’s affairs in months.

"She's been the total enabler. She would go after these women and destroy their lives," Trump said. "She was an unbelievably nasty, mean enabler, and what she did to a lot of those women is disgraceful."

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His comments came as part of a defense against recent attacks from Democrats focused on his controversial comments and stances on women’s issues. Trump told the crowd “nobody respects women more than me,” but in contrast, “nobody in this country, and maybe in the history of the country politically, was worse than Bill Clinton with women.”

“Have you ever read what Hillary Clinton did to the women that Bill Clinton had affairs with? And they’re going after me with women?” he added, incredulously, without citing any specific examples or sources.

While it was his most caustic attack against the presumptive Democratic nominee on Friday night, it was by no means the only line of attack he opened against Clinton. He charged that she would be “sleeping” when national security crises hit at odd hours, tied her to NAFTA, and called her a “tool of Wall Street.” He also said he was the “last person she wants to run against…because my attitude is, I don’t care.”

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Trump also took sharp aim at Democratic Sen. Elizabeth Warren, the liberal darling who’s been the subject of vice-presidential chatter in recent weeks, with whom Trump’s opened up a feud over social media in recent days.

In front of a crowd of thousands on Friday night, Trump unveiled a new nickname for the Massachusetts senator: “Goofus.”

Clinton’s “got this goofy friend Elizabeth Warren, she’s on a Twitter rant, she’s a goofus,” he said.

“This woman, she’s a basketcase. By the way, she’s done nothing in the United States. She’s done nothing.”

“Goofy,” @realDonaldTrump? For a guy with "the best words" that’s a pretty lame nickname. Weak! — Elizabeth Warren (@elizabethforma) May 7, 2016

He suggested Clinton choose Warren as her running mate because “without that [woman] card she would get nobody voting for her.”

Trump toned down his attacks on members of his own party considerably, but still doled them out to his most recent critics, calling Jeb Bush “low-key — “I wanted to say ‘low-key’ cause its nicer than saying ‘low-energy,’” he joked — and telling the crowd Sen. Lindsey Graham “knows less about the military than my 10 year old son Barron.”

Both Graham and Bush have refused to support Trump in the days since he became the last man standing in the GOP primary, even as other Republicans have fallen in line.

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Trump also dismissed House Speaker Paul Ryan’s refusal to back him as Paul simply “trying to be cute,” noting they previously had a very pleasant phone conversation three weeks ago.

But mostly, Trump seemed tickled, if also somewhat chagrined, by the fact that many of the remaining holdouts signed a pledge from the Republican National Committee promising to back the eventual nominee — a ploy initially used by the RNC to ensure Trump wouldn’t launch a third-party bid.

“I signed a pledge, and they’re the ones that are violating it!” he said.

He dismissed, however, the holdouts, telling the crowd he “released” them.

“If somebody doesn’t wanna endorse, I don’t want their endorsement,” he said.

Trump delivered the speech, his second of the day, in deep-blue Oregon to a backdrop of protests bubbling outside and a few scattered protests inside. Despite their best efforts to goad Trump supporters into a confrontation — protesters shouted “Racist!” and “Heil Trump!” at supporters as they walked through the gates — the protests went off peacefully, with police keeping them far away, and blocked off by a fence, from the arena.

But despite the blue tint of the state, Trump promised to win it in the general.

“We are going to carry your state in November,” he said, to cheers from the crowd.