"It is really important to remain skeptical here," Panetta said. "The reality is that it’s the supreme leader that ultimately determines what will or will not happen."
Panetta said U.S. intelligence on Supreme Leader Ali Khamenei indicates he is "very anti-American" and "very concerned about establishing any relationship with the United States."
"He is still the power there," Panetta cautioned, at a breakfast hosted by The Wall Street Journal.
He also said he remains skeptical that Syrian President Bashar Assad will actually give up his chemical weapons.