Eyewitness accounts and evidence collected from Syria's northwestern Idlib province "strongly" suggest regime forces dropped toxic chemicals on civilians several times last month, Human Rights Watch said Tuesday.
A high-ranking Syrian security official denied the claim, saying the accusations were "lies the insurgents say when they incur losses".
The report came as a monitor said at least 12 people were killed on Tuesday in a barrel bomb attack in the province.
Human Rights Watch said the chemicals appeared to have been packed into crude explosives-filled barrels that were dropped by military helicopter on rebel-held areas during heavy fighting for Idlib city.
"Evidence strongly suggests that Syrian government forces used toxic chemicals in several barrel bomb attacks in Idlib governorate between March 16 and 31, 2015," the New York-based group said.
It called on the UN Security Council to investigate what would be a breach of both its own resolutions and Damascus's obligations under the Chemical Weapons Convention.
HRW said it had investigated six reported attacks in Idlib and villages outside, collecting evidence from rescue workers and other civilians that provided a compelling case in three of them.
The most conclusive evidence came from a March 16 attack on the village of Sarmin, which left a family of six, including three children, dead, and an attack on Idlib city on March 31.
"The children were foaming at the mouth, they were suffocating, then their hearts stopped," said Leith Fares, a rescue worker in Sarmin.
HRW said it could not conclusively establish the chemical used, but volunteers from the Syrian Civil Defence said they found remnants of barrel bombs at attack sites and smelled chlorine gas on victims' clothes.
The Syrian security official told AFP these were lies that rebels spread to "explain their failures to their funders".
"If the army used chemical weapons or chlorine gas every time they say it did, those people would have been completely wiped out by now," he said.
The world's chemical weapons watchdog had already expressed "serious concern" on March 25 over the reported use of toxic agents in Idlib province.
In January, it reported the use of chlorine gas in attacks on three Syrian villages last year.
The Organisation for the Prohibition of Chemical Weapons did not attribute responsibility for those attacks, although its report cited witnesses saying they heard helicopters, which only the regime possesses.
In early March, the UN Security Council adopted a US-drafted resolution condemning the use of chlorine in Syria and threatening sanctions if the chemicals were used again.
"The Syrian government appears to be thumbing its nose at the Security Council and international law yet again," HRW deputy Middle East director Nadim Houry said.
Damascus did not have to declare its stocks of chlorine under a 2013 agreement to dismantle its chemical arsenal, as the substance is widely used for commercial and domestic purposes.
But using the gas for military purposes would be a breach of its undertakings under the Chemical Weapons Convention, which it signed as part of the deal.
Meanwhile, the Syrian Observatory for Human Rights, a Britain-based monitor, reported at least 12 people were killed Tuesday in a barrel bomb attack on the town of Saraqeb in Idlib province.
The group said the toll was expected to rise because a number of the wounded were in a serious condition.
And in the southern province of Daraa, at least six children were killed in barrel bomb attacks on Al-Krak, the Observatory said.
On the political front, the UN said its envoy Staffan de Mistura wants his next consultations on the Syria conflict, due to be held next month in Geneva, to include "all those with influence".
UN spokesman Stephane Dujarric, pressed by reporters, refused to say whether Damascus ally Iran would or should be invited to the talks.
More than 215,000 people have been killed in Syria since the conflict began with anti-government protests in March 2011 that spiralled into a war after a regime crackdown.