The Islamic State group says it carried out bomb attacks in the Syrian capital Damascus and the city of Homs, which left at least 140 people dead.
Four blasts in the southern Damascus suburb of Sayyida Zeinab killed at least 83 people, state media say.
Earlier in Homs, 57 people, mainly civilians, were killed in a double car bombing, a monitoring group reports.
Both of Sunday's attacks targeted areas dominated by Islamic minorities reviled by the Sunni Muslim radicals of IS.
The blasts came as President Bashar al-Assad told reporters Syrian refugees should not be scared of returning home.
Mr Assad, who has long been accused of persecuting his own people, said ordinary Syrians who had fled the conflict due to the "standard of living that has been deteriorating drastically" could go back without fear of action by the government.
"We want people to come back to Syria," he told reporters.
More than 250,000 Syrians have been killed in the conflict. Some 11 million others have been forced from their homes, of whom four million have fled abroad - including growing numbers who are making the dangerous journey to Europe.
Earlier, US Secretary of State John Kerry said a "provisional agreement" had been reached with Russia on a partial truce.
However he admitted issues remained to be resolved and said he did not expect any immediate change on the ground.
Earlier this month, world powers involved in the crisis in Syria agreed to seek a "cessation of hostilities", but the Friday deadline came and went.
In Damascus on Sunday, the state-run Sana news agency reported least 83 dead and 178 wounded in several explosions in Sayyida Zeinab. It is the location of Syria's holiest Shia Muslim shrine, said to contain the grave of the Prophet Muhammad's granddaughter.
The Amaq news agency, which is linked to IS, said IS militants had detonated a car bomb and then blown up explosive belts.
Muhannad, a local resident, told Reuters news agency he was sleeping in his home when he heard an explosion.
"A man detonated the bomb on his body," he said.
"Another five to seven minutes later, a second man detonated his body bomb there. I was right here looking at him."
The district was hit by suicide attacks last month that left 71 people dead and which IS fighters also said they had carried out.
In Homs, the blasts happened in a predominantly Alawite district, the sect to which President Bashar al-Assad belongs.
One of the early centres of the uprising against President Assad, Homs was once dubbed the "capital of the revolution".
But rebels left the city late last year under a ceasefire deal, leaving the city in government hands.
Sunday's attacks came as warring factions waged fierce battles for the northern city of Aleppo.
The UK-based Syrian Observatory for Human Rights monitoring group also said that at least 50 Islamic State fighters had been killed in an advance by government troops, backed by Russian air strikes, east of the city in the past 24 hours.
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