Denouncing the crackdown on supporters of ousted president Mohamed Morsi, Kerry urged a "peaceful, democratic way forward."
"Today's events are deplorable and they run counter to Egyptian aspirations for peace, inclusion and genuine democracy," Kerry told reporters.
"The interim government and the military -- which together possess the preponderance of power in this confrontation -- have a unique responsibility to prevent further violence and to offer constructive options for an inclusive peaceful process across the political spectrum," Kerry said.
"All parties also share a responsibility to avoid violence and to participate in a productive path towards a political solution," he said, pointing to the opposition.
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Kerry said that a political solution was the only option but acknowledged: "It has been made much, much harder and much, much more complicated by the events of today."
More than 120 people were killed when security forces broke up gatherings by supporters of Morsi, according to an AFP correspondent who visited makeshift morgues.