President Barack Obama had a tough message for the American Israel Public Affairs Committee, or AIPAC, the powerful pro-Israel group that is furiously campaigning against the Iran nuclear accord, when he met with two of its leaders at the White House this week. The President accused AIPAC of spending millions of dollars in advertising against the deal and spreading false claims about it, people in the meeting recalled.

So Mr. Obama told the AIPAC leaders that he intended to hit back hard.

The next day, in a speech at American University, Mr. Obama denounced the deal’s opponents as “lobbyists” doling out millions of dollars to trumpet the same hawkish rhetoric that had led the U.S. into war with Iraq. The President never mentioned AIPAC by name, but his target was unmistakable.

The remarks reflected an unusually sharp rupture between a sitting U.S. President and the most potent pro-Israel lobbying group, which was founded in 1951 a few years after the birth of Israel. Ronald Reagan opposed AIPAC when he defied Israeli objections over the sale of AWACS reconnaissance planes to Saudi Arabia in 1981. A decade later, George H.W. Bush took on the group during a fight over housing loan guarantees for Israel, saying he was just “one lonely little guy” going up against a thousand lobbyists on Capitol Hill.

But the tone of the current dispute is raising concerns among some of Mr. Obama’s allies who say it is a new low in relations between AIPAC and the White House. They say they are worried that, in working to counter AIPAC’s tactics and discredit its claims about the nuclear accord with Iran, the President has gone overboard in criticising the group and like-minded opponents of the deal.

“It’s somewhat dangerous, because there’s a kind of a dog whistle here that some people are going to hear as ‘it’s time to go after people’, and not just rhetorically,” said David Makovsky, a former Middle East adviser for the Obama administration and now an analyst at the Washington Institute for Near East Studies. But AIPAC’s rhetoric, he said, had been just as overheated. “There’s almost a bunker mentality on both sides.”

Mr. Obama’s advisers strongly disputed the suggestion that he used coded language to single out AIPAC when he said in his American University speech that “many of the same people who argued for the war in Iraq are now making the case against the Iran nuclear deal.”

“This has nothing to do with anybody’s identity; this is a policy difference about the Iranian nuclear program,” said Benjamin J. Rhodes, the deputy national security adviser for strategic communications.

“We don’t see this as us versus them,” Rhodes added, predicting that the White House and AIPAC would work closely on other matters, including Israeli security. “This is a family argument, not a permanent rupture.”

But for now, the struggle is critical for Obama, who regards the agreement — which lifts some sanctions against Iran in exchange for restrictions aimed at restraining its ability to obtain a nuclear weapon — as a landmark achievement. He is fighting to rally enough Democratic support to preserve the deal before a September vote on it in the Republican-led Congress.

AIPAC is working to deny him that by leaning hard on Democrats, including Sen. Chuck Schumer of New York, who on Thursday announced his opposition.

The group had sent 60 activists to Schumer’s office to lobby him last week, while Citizens for a Nuclear Free Iran, an offshoot AIPAC formed to run at least $25 million in advertising against the deal, ran television spots in New York City. — New York Times News Service