Washington accused Manssor Arbabsiar and Gholam Shakuri of allegedly seeking the help of a Mexican drug cartel in a plot to assassinate the Saudi envoy to the United States.
Arbabsiar was accused of acting on behalf of the Iranian government when he tried to hire a Mexican cartel member, who was an informant for the U.S. Drug Enforcement Administration.
U.S. Vice President Joe Biden told CBS News that if the allegations prove correct, the consequences for Iran "will be serious."
The assassination of Jubeir was said to be planned on U.S. soil.
Counter-terrorism analysts said the claims of Iranian plots inside the United States are unusual. Richard Clarke, a former counter-terrorism official inside the White House, told National Public Radio that it was curious that the Iranians would work through a Mexican drug cartel.
"This is a really strange plot," he said.
Tehran announced Wednesday that it summoned the Swiss envoy to protest the U.S. allegations. The Iranian Foreign Ministry, in statements published by Press TV, said the U.S. claims were politically motivated.
Ali Larijani, the speaker of the Iranian Parliament, said Washington was taking part in a "childish game."
Stratfor, a private intelligence company in Texas, said the while Iran is known to conduct intelligence operations in the United States, it hasn't used the information to carry out attacks.