Trusting the US would be "a big mistake," said Supreme Leader Ayatollah Ali Khamenei, insisting that cooperation with America goes "against the independence" of Iran.
There has been no formal talk of a joint fight or even cooperation between Iran and the United States against the Islamic State group. Nevertheless, Khamenei's remarks were somewhat ironic since the war against the Islamic State has put Americans and Iranians in close proximity.
But Khamenei said that despite the nuclear deal which went into effect this year, Iran has "many small and big enemies, but foremost among them are America," Britain and Israel.
He spoke at a ceremony marking the 27th anniversary of the death of Ayatollah Ruhollah Khomeini, the leader of the 1979 Islamic Revolution that brought hard-line clerics to power and ousted the US-backed Shah Mohammad Reza Pahlavi.
The deal with world powers eased Tehran's isolation from the international community and removed many economic sanctions in exchange for Iran curtailing its nuclear programme.
But the agreement, struck in 2015 with moderate President Hassan Rouhani's administration, has been assailed by Iranian hard-liners, and in the months since its implementation, Iran has conducted missile tests criticised by the US, as well as aired footage on state television of an underground missile base.
In Syria, Shiite power Iran is a top backer of President Bashar Assad, along with Russia. Tehran has deployed what it says are military advisers to support the Syrian government and has had casualties in the conflict, though it denies the presence of Iranian combat troops.
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