The claims came as a 20-member U.N. chemical weapons team was in Syria to investigate three sites where chemical weapons attacks had allegedly occurred in the past.
The Syrian government promptly denied the reports of Wednesday's chemical weapons' attack as baseless.
"They are an attempt by to divert the U.N. commission on chemical weapons from carrying out its mission," the state-run SANA news agency said, quoting an unnamed government official, as is its standard practice.
The Britain-based Syrian Observatory for Human Rights said the shelling was intense and hit the capital's eastern suburbs of Zamalka, Arbeen and Ein Tarma.
It quoted activists as saying that regime forces fired "rockets with poisonous gas heads" in the attack that killed "tens of people."
Rami Abdul-Rahman, the Observatory chief, said the activists in the area said "poisonous gas" was fired in rockets as well as from the air. He added that regime forces were on a wide offensive on the eastern and western rebel-held suburbs of Damascus.
Another group, the Local Coordination Committees, said hundreds of people were killed or injured in the shelling. Such different figures from activists groups are common in the immediate aftermaths of attacks in Syria, where the government restricts foreign and domestic reporting.
Abdul-Rahman said more than 40 people have been confirmed dead and that the death toll could reach as many as 200 in the suburbs of Damascus.
The Syrian government has long denied claims by the opposition on chemical weapons use, saying rebels fighting to overthrow President Bashar Assad's government have used such weapons.
Following Wednesday's reports, the Observatory called upon the U.N. team in Syria and all international organizations "to visit the stricken areas and to guarantee that medical and relief supplies reach the people as soon as possible." It also called for an investigation into the attack.
Mohammed Saeed, an activist in the area, told The Associated Press via Skype that hundreds of dead and injured people were rushed to six makeshift hospitals in the eastern suburbs of Damascus.
"This is a massacre by chemical weapons," said Saeed. "The visit by the U.N. team is a joke ... Bashar is using the weapons and telling the world that he does not care."
The U.N team, led by Swedish expert Ake Sellstrom, is meant to probe three sites: the village of Khan al-Assal just west of the embattled northern city of Aleppo and two other locations, which are being kept secret for security reasons.
Wednesday's claim of the chemical attack, if confirmed, would be the most serious since the March 19 incident in Khan al-Assal when at least 30 people were killed. Assad's regime and the rebels have blamed each other for that attack.
Unrest in Syria began in March 2011 and later exploded into a civil war. More than 100,000 people have been killed in the conflict.
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