The editor-in-chief of the reformist news network Nazar, Payam Parhiz, wrote on Twitter that it was not clear what person or group organised the protest in Mashhad. Protesters also waved banners denouncing Iran's interference in the Arab region, chanting "forget about Syria, think about us".
Nazar and the semi-official Ilna news agency reported that there were also smaller protests on Thursday in Neyshabour, Kashmar, Yazd and Shahroud. Demonstrators reportedly gathered to protest rising prices in the country, alleged corruption in the government and Iran's involvement other in regional conflicts.
Rouhani's first vice-president, Eshaq Jahangiri, dismissed the demonstrations in a speech on Friday, and said economic issues were "being used as an excuse and something else, behind the curtain, is going on", the Iranian Students News Agency reported.
The U.S. State Department released a statement strongly condemning the arrest of peaceful protesters.
It's the first wave of mass protests in Iran in nearly a decade. "As President Trump has said, the longest-suffering victims of Iran's leaders are Iran's own people", said State Department spokesperson Heather Nauert.
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Videos posted online showed a crowd in Mashhad chanting "Death to the dictator" and "Death to Rohani", with police using water cannons to push back the crowds.
The last unrest of national significance occurred in 2009 when Mahmoud Ahmadinejad's re-election as president ignited eight months of street protests.
Protesters raised the slogans "Death to Rouhani, and Death to the Dictator".
Prices on many essential products, including eggs, have increased up to 40 percent in recent days. They also played a significant role in keeping the protests going.
Tehran-based analyst Saeed Leilaz told The Associated Press on Thursday that Rouhani's political rivals may have played a role in organizing the protests.