President Biden’s declaration that Russian leader Vladimir Putin “cannot remain in power” threatens to push deeply strained U.S.-Russia relations closer to collapse, former officials and analysts said, with potentially serious implications for Washington’s ability to help steer the war in Ukraine to an end and avoid a wider conflict.

The remark – an off-the-cuff coda to an address in Poland this weekend – injects a stark new element of personal animus into the standoff between the world’s biggest nuclear powers. It capped earlier statements in which Biden has gone well beyond official formulations – calling Putin a “killer,” “butcher” and “war criminal.”

Samuel Charap, a Russia expert at the RAND Corporation, said the administration’s attempts to walk back the suggestion of a U.S. goal of regime change would do little to alter views in Moscow because Putin has long believed the United States is out to replace him and presidential statements have traditionally been seen as official policy.

“It exacerbates existing threat perceptions regarding U.S. intentions,” he said. “They might just be much more inclined to do hostile things in response even more than they already are. That is the challenge.”

Biden’s speech came at the conclusion of a European visit designed to prepare allies for a prolonged campaign of economic punishment targeting Russia, requiring difficult political and financial decisions from leaders on the continent, as Putin’s invasion stalemates in the face of Ukrainian resistance.

Biden’s speech at a castle in Warsaw, which came hours after an emotional encounter with Ukrainian refugees, was intended to telegraph Western resolve against Russia’s actions and, more broadly, the forces of autocracy worldwide. It echoed moments in which U.S. leaders have cast their standoff with Moscow in sweeping, moral terms, including Ronald Reagan’s 1983 address depicting the Soviet Union an “evil empire.”

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U.S. officials said a day after the speech that they had no specific expectations about Russian retaliation and downplayed the significance of the president’s remark in light of recent U.S. actions that have already antagonized Moscow, including unprecedented financial sanctions and more than $2 billion in security aid for Ukraine over the last month.

Last week, Secretary of State Antony Blinken announced an official assessment that Russian forces are committing war crimes in Ukraine, raising the possibility of U.S. backing for an eventual war crimes trial targeting Putin, as his military’s commander in chief.

Russia’s initial response to Biden’s statement was relatively muted, with Kremlin spokesman Dmitry Peskov saying of Putin’s political future: “That’s not for Biden to decide. The president of Russia is elected by Russians.”

But the remark is sure to reaffirm the Russian leader’s long-standing conviction that the United States would like to push him from power. That notion dates at least to 2011, when then-Secretary of State Hillary Clinton suggested Russian elections had been rigged, and Putin, serving as prime minister at that time, accused the United States of fomenting protests against the vote.

“Putin has been paranoid about the West seeking ‘regime change’ against his government for a long time,” said Michael McFaul, who served as U.S. ambassador in Moscow during the Obama administration.

Biden’s comment nevertheless raises the specter of an emotional response from Putin, who American officials say is increasingly isolated as he grapples with the collapse of the Russian economy and the reality of his unexpectedly difficult military campaign.

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Analysts said that any Russian response was most likely to come in the diplomatic realm, where a steady stream of actions has already narrowed the channels the two countries use to communicate. Just last week, the Kremlin notified the State Department that it was moving to expel an additional tranche of American diplomats in Moscow, in a move that pushes the U.S. mission there closer to having to shut down. Also this month, the Kremlin summoned Washington’s ambassador, John Sullivan, to reprimand him over Biden’s “war criminal” remark.

If Moscow decided to throw out the remaining U.S. diplomats, it would mark a diplomatic low that was avoided even during the worst moments of the Cold War. When Soviet leader Joseph Stalin expelled U.S. Ambassador George Kennan in 1952 for likening conditions in Moscow to what occurred in Nazi Germany, the U.S. Embassy remained open.

Biden has not spoken to Putin since the Russian leader launched his invasion on Feb. 24; neither has Blinken talked to Foreign Minister Sergei Lavrov. Recent efforts by Pentagon leaders to reach their Russian counterparts have likewise been rebuffed, raising concerns about military miscalculation.

Russia also has the potential to resort to a less visible response. The White House has issued a stepped-up warning about the potential for Russia to mount cyberattacks. If such an action occurs, it would be difficult for American officials to know whether it was taken as a calculated response to Western sanctions or out of pique over Biden’s comment.

Biden’s declaration has also deepened questions about the United States’ ability to facilitate a peaceful end to the conflict, which has already unleashed a wave of more than 3 million refugees and exacted a brutal price on civilians remaining in Ukraine.

While the United States has no direct mediation role between Kyiv and Moscow – as France, Israel, Turkey and other countries seek to advance avenues for diplomacy – its role as NATO’s most powerful member and the orchestrator of Western sanctions means that a full U.S.-Russian rupture could have far-reaching effects. Experts pointed out that an eventual peace deal would likely require presidential communication between Washington and Moscow.

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French President Emmanuel Macron suggested that Biden’s comment did not sit well with all leaders in Europe. “If we want to do that, we can’t escalate either in words or actions,” he said of the odds for diplomatic success.

In Washington, the remark was likewise met with Republican criticism. Sen. James Risch, R-Idaho, ranking Republican on the Senate Foreign Relations Committee, called it a “horrendous gaffe.”

“I think most people who don’t deal in the lane of foreign relations don’t realize that those nine words that he uttered would cause the kind of eruption they did,” Risch said on CNN. “Anytime you say, or even as he did suggest, that the policy was regime change, it’s going to cause a huge problem.”

Some former officials said they expect minimal effect on Putin’s calculus in Ukraine, which is predicated primarily on Putin’s sense of Russia’s national interest and his need to avoid a humiliating military defeat.

“He will escalate or not based on his assessments of fighting on the ground,” McFaul said.

Daniel Fried, a retired diplomat who served as the State Department’s top diplomat for Europe, said that American “solicitude for Putin’s feelings” hadn’t succeeded in altering the Russian leader’s actions in the past.

“Given what Putin is doing, I think Biden was right to call it out,” he said. “He wasn’t making an operational policy statement. He was making a moral one, and there’s a difference.”

The Washington Post’s John Hudson in Jerusalem and Paul Sonne in Washington contributed to this report.

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