Volunteer rescue force the White Helmets tweeted graphic images showing several bodies in basements. It said the deaths were likely to rise.
There has been no independent verification of the reports.
Syria's government has called the allegations of a chemical attack a "fabrication".
The US state department said reports suggested "a potentially high number of casualties", including families in shelters.
It said Russia - with its "unwavering support" for Syria's government - "ultimately bears responsibility" for the alleged attacks.
"The regime's history of using chemical weapons against its own people is not in dispute," it said in a statement.
Footage on social media purported to show children being treated for the effects of the attack
What do we know about the attack?
Several medical, monitoring and activist groups reported details of a chemical attack, but figures vary and details of what happened are still emerging.
"Seventy people suffocated to death and hundreds are still suffocating," said Raed al-Saleh, head of the White Helmets. An earlier, now deleted tweet, put the number dead at more than 150.
The pro-opposition Ghouta Media Center tweeted that more than 75 people had "suffocated", while a further 1,000 people had suffered the effects of the alleged attack.
It blamed a barrel bomb allegedly dropped by a helicopter which it said contained Sarin, a toxic nerve agent.
The Union of Medical Relief Organizations, a US-based charity that works with Syrian hospitals, the Damascus Rural Specialty Hospital had confirmed 70 deaths.
Pro-government forces are fighting to drive rebels out of Douma
A spokeswoman said reports on the ground suggested a much higher number of around 180 dead, but that it was hard to reach victims due to continuous shelling and the time of night.
She said there were reports of people being treated for symptoms including convulsions and foaming of the mouth, consistent with nerve or mixed nerve and chlorine gas exposure.
As the allegations emerged, Syria's state news agency Sana said the reports were invented by the Jaish al-Islam rebels who remain in control in Douma.
"Jaish al-Islam terrorists are in a state of collapse and their media outlets are [making] chemical attack fabrications in an exposed and failed attempt to obstruct advances by the Syrian Arab army," Sana said.
Has the Syrian government used chemical weapons before?
In August 2013, rockets containing the nerve agent Sarin were fired at rebel-held areas of the Eastern Ghouta, killing hundreds of people.
A UN mission confirmed the use of Sarin, but it was not asked to state who was responsible. Western powers said only Syrian government forces could have carried out the attack.
In April 2017, more than 80 people died in a Sarin attack on the opposition-held town of Khan Sheikhoun, and a joint inquiry by the UN and the Organization for the Prohibition of Chemical Weapons (OPCW) held the Syrian government responsible.
About 80 people died and many more were injured in the attack on Khan Sheikhoun
Activists, medics and the US say Syrian government forces dropped bombs containing toxic chlorine gas on rebel-held towns in early 2018.
The joint UN-OPCW mission is investigating the reports. It previously found that government forces have used chlorine as a weapon at least three times during the seven-year civil war.
What's happening in Douma?
Douma is the last rebel-held town in Syria's Eastern Ghouta region, and is under siege from Russian-backed Syrian government forces.
An intense aerial and ground assault was launched on Friday after talks between Moscow and the rebels broke down.
Before negotiations failed, Jaish al-Islam had been trying to secure a deal that would let its members stay in Douma as a local security force.
The UK-based Syrian Observatory for Human Rights, a monitoring group, said government air strikes had killed 40 civilians on Friday, and a further 30 on Saturday.
State media said six civilians had also died in rebel shelling of the capital Damascus, with 38 injured. Jaish al-Islam denied it was responsible.
Syrian state media said civilians in the suburbs of Damascus had been killed and injured by rebel mortar fire
Forces loyal to Syria's President Bashar al-Assad have recaptured almost the entire Eastern Ghouta region through a fierce offensive that started in February.
More than 1,600 people are reported to have been killed and thousands injured.