Sixteen Islamist activists were shot dead early on Monday during a protest outside a key Cairo army headquarters calling for ousted president Mohamed Morsi to be reinstated, his Muslim Brotherhood said.
"Sixteen people were killed and 100 others injured, many of them in serious condition," the group's spokesman Ahmed Aref told AFP.
Demonstrators told AFP that troops and police had fired tear gas canisters and bullets into the air to disperse the protesters.
"They wanted to disperse the protesters," who were determined to stage an indefinite sit-in, the protester said.
Another protester, Mahmud al-Shilli confirmed that security forces fired into the air, adding that a group of men in civilian clothing had attacked the protesters.
"The Republican Guard fired tear gas but the thugs came from the side. We were the target," Shilli told AFP.
Earlier, demonstrators told AFP by telephone that troops and police had fired tear gas canisters and live rounds in a bid to disperse them.
"I saw with my own eyes the people who they shot at," one protester said, adding that several people had been injured.
On Friday at the same spot, four Islamists were shot dead by soldiers.
Supporters of Morsi's Muslim Brotherhood have mobilised in large numbers in different parts of Cairo in recent days, vowing to defend Morsi, who was ousted by the military on Wednesday after mass protests calling for him to be removed from power.
Morsi was Egypt's first freely elected president but lasted just a year in power.