The White House on Monday denounced efforts by Republican lawmakers to "throw sand in the gears" of sensitive talks over Iran's nuclear program as "partisan."
Forty-seven Republicans, including Senate leaders and several potential 2016 presidential candidates, wrote an open letter to Iran's leader, warning any deal with President Barack Obama might not be honored in future.
The White House responded angrily, accusing the Senators of interference and continuing a "partisan strategy to undermine the president's ability to conduct foreign policy and advance our national security."
"It raises significant questions about the intent or the aims of the authors," said spokesman Josh Earnest, who accused the senators of establishing a "back channel" with hardliners in Tehran.
With a March deadline looming, negotiators are furiously working to agree a deal that would curb Iran's nuclear program in return for reducing Western sanctions.
The deal is seen as a key foreign policy goal of the Obama administration.
Earnest also accused Republicans of supporting airstrikes against Iran's facilities that the White House says would only temporarily set Iran's program back.
"The rush to war, or at least the rush to the military option that many Republicans are advocating, is not at all in the best interests of the United States," said Earnest.
He said the senators' actions were not in keeping with the role that America's founding fathers envisioned for the legislative branch.