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Speaking to air force commanders in Tehran on Thursday, Ayatollah Ali Khameini said Iran "will not negotiate under pressure."

Caren Firouz/Reuters

Ayatollah Ali Khamenei said Tehran would not be intimidated by Washington.

"The Iranian nation will not negotiate under pressure," Ayatollah Khamenei said. Noting the international sanctions against Iran, which were bolstered on Wednesday by new American financial restrictions that essentially reduce Iran to using its oil for barter trade, he added: "The U.S. is pointing a gun at Iran and wants us to talk to them. The Iranian nation will not be intimidated by these actions."

"Direct talks will not solve any problems," he concluded.

His statement was considered particularly important because, as one senior Obama administration official put it, "we believe Khamenei now holds the entire nuclear file."

But the White House did not immediately react to the statement, and some officials said that history — including during the Iran-Iraq war — demonstrates that Iran can change its position quickly. Despite the ayatollah's comments, it appears that talks scheduled to begin Feb. 26 between Iran and six nations, including the United States, will go ahead in Kazakhstan.

But American officials have said repeatedly in recent months that they believe negotiating in that multinational forum can be awkward, partly because of differences with Russia and China over Tehran. That is one reason Vice President Joseph R. Biden Jr. went to a security conference in Munich last weekend to publicly reinforce President Obama's private offer of direct talks.

It was at that conference that the Iranian foreign minister, Ali Akbar Salehi, said he was open to such talks, although Mr. Biden noted that they could proceed only if the ayatollah showed serious interest. Mr. Salehi had been one of Iran's top nuclear negotiators, and while he has often projected a moderate tone, he has also made it clear that his authority is limited. An effort to negotiate a deal early in Mr. Obama's presidency resulted in an agreement that Ayatollah Khamenei rejected.

The ayatollah's objection is an edict to which other Iranian officials, including President Mahmoud Ahmadinejad, must adhere, and it comes after several high-ranking Iranian officials, including Mr. Ahmadinejad and Mr. Salehi, said that the Obama administration had been taking positive steps toward Iran. Ayatollah Khamenei's wording was quite direct in his speech before air force commanders at his Tehran office, and his comments were reported on his personal Web site.

"I'm not a diplomat; I'm a revolutionary, and speak frankly and directly," he said. "If anyone wants the return of U.S. dominance here, people will grab his throat."

He said that while some "simple-minded people" might be eager for the prospect of bilateral talks, Iran had seen nothing from the Obama administration other than conspiracies. Those comments are in accord with American intelligence assessments of the supreme leader's views, which include, officials say, a belief by the ayatollah that the sanctions are hurting the United States more than they are hurting Iran.

Other officials close to the ayatollah have said in recent days that the real goal of America's negotiations, the sanctions and the sabotage of Iran's nuclear facilities is to bring down the Iranian government.

Under the new restrictions on Iranian oil payments announced Wednesday, when countries still buying Iranian oil pay for their purchases, the money must be put into a local bank account, which Iran can use only to buy goods within that country. It is a way of keeping the money from being transferred to Iran, and the Treasury Department said on Thursday that it would strictly enforce the provisions, barring any banks that violate the new sanctions from conducting transactions with the United States.

In Tehran, the comments were met with some sense of resignation — and suggestions that Mr. Obama's openness to negotiation was a ploy, intended to set international opinion against Iran.

"There is no room for any optimism," said Hamid Reza Taraghi, an influential politician. Pointing to the new sanctions, decisions by American courts to seize Iranian assets and the American support for the opposition in Syria, where President Bashar al-Assad is Iran's last regional ally, he said, "We haven't seen anything good from the U.S."

Iran experts outside the country said they were not surprised that Ayatollah Khamenei had ruled out dialogue with the United States, given his longstanding antipathy toward the Americans.

"This is expected from Khamenei; his ideological view of the United States is getting in the way," said Alireza Nader, a senior policy analyst at the Washington offices of the RAND Corporation. "Khamenei may be reluctant to negotiate — perhaps he does not want to from a weak position — but his hand is going to get weaker as time goes by."

Trita Parsi, the author of a critical account of the Obama administraton's diplomacy with Iran, "A Single Roll of the Dice" (Yale University Press, 2012), wrote in a post Thursday on The Daily Beast that the ayatollah sees little advantage in breaking the current stalemate.

"As long as the West does not put offers on the table that meet Iran's bottom line, the calculation goes, Iran should play for time and seek a game changer that enables it to set the terms for a deal," he wrote.

"Even though the price of stalling will be high, the price of failed talks will likely be equally high, leaving Tehran better off seeking to press the West to improve the deal — rather than participating in talks that are doomed to fail."

Thomas Erdbrink contributed reporting from Tehran, and Rick Gladstone from New York.