The agreement, announced yesterday, does not apply to jihadists like the Islamic State group and Al-Nusra Front, putting up major hurdles to how it can be implemented on Syria's complex battlefield.
A Syrian foreign ministry statement said the government would continue to fight both those groups as well as other "terrorists", while agreeing to stop other military operations "in accordance with the Russian-American announcement."
The deal calls for a "cessation of hostilities" between forces loyal to President Bashar al-Assad and opposition groups that would take effect overnight Friday-Saturday in Damascus.
But after several previous failed attempts, few had serious expectations for a lasting ceasefire.
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Analysts said the deal may be simply unworkable, rebels on the ground doubted the regime's goodwill and many civilians expected their hopes to once again be dashed.
"It's a waste of time and it's difficult to implement on the ground," said Abu Ibrahim, a commander in the 10th Brigade opposition force in the northwestern Latakia province.
He expected "numerous rebel groups" to reject the agreement, which he said was formed "without consulting any factions on the ground."
In Damascus, residents tired after nearly five years of war were also deeply sceptical.
"It's a fragile deal," said Rana, a 54-year old pharmacist in the capital.
"Ceasefires have been announced repeatedly in the past and we didn't see any results on the ground because they were violated," she said.
Despite being on opposing sides of the conflict, Moscow and Washington have been leading the latest diplomatic push to try to resolve a conflict that has left more than 260,000 dead and forced millions from their homes.
Russia says it is targeting "terrorists" in its strikes but has been accused of hitting non-jihadist groups in support of Assad, a longtime ally.