The 6-mile-long downtown Enghelab, or Revolution Street, in Tehran was decorated with huge balloons as loudspeakers blared out revolutionary and nationalist songs to encourage people to join the rallies.
Some of the protesters burned USA flags.
Tensions between Washington and Tehran are high after the United States withdrew from an worldwide nuclear deal aimed at curbing Iran's nuclear ambitions, and re-imposed sanctions that have hurt the Iranian economy.
Washington and its Arab allies have viewed Iran with great suspicion since the Islamic Revolution, fearing Khomeini's radical ideology would inspire militants across the Middle East.
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President Donald Trump slammed Iran's Islamic revolution as a complete failure for the country in tweets written in both English and Farsi Monday on the 40th anniversary of the Iranian Revolution.
Iran even holds an annual "Death to America" rally every November to commemorate the seizure of the U.S. Embassy in 1979, leading to a 444-day hostage crisis in which the Iranian regime held 52 Americans prisoner. "The Iranian people have and will have some economic difficulties but we will overcome the problems by helping each other", he said.
State television offered blanket coverage of the commemorations, showing marches in cities ranging from Abadan in southwestern Iran to Mashhad in the northeast.
In Tehran, 27-year-old medical student Hossein Hosseinpour, walked with his wife and their 18-month son Amir Ali. "My mother, despite her illness, asked me to bring her out", he said. "I don't think you'll have many more anniversaries to enjoy", Bolton concluded.
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One sign read, "Much to the dismay of America, the revolution has reached its 40th year".
Trump was echoed by National Security Adviser John Bolton, who published a spate of tweets, in which he argued in particular that "the 40th anniversary of the Iranian regime only serves to highlight four decades of failure and broken promises".
The Iranian people "will not stop saying "Death to America" as long as the USA acts malicious" toward Iran, Khamenei said, referring to Trump's State of the Union address in which the American president, among other things, said: "We will not avert our eyes from a regime that chants death to America".
Pahlavi's name has been in the news often since late 2017 as some groups in Iran have called for a return of the monarchy during large nationwide demonstrations against political corruption and poor economic conditions.
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