The shock attack comes despite a Russian air campaign targeting the group that began in September, and more than a year of strikes by a US-led coalition against the jihadists in Syria.
The Britain-based Syrian Observatory for Human Rights said IS had killed at least 135 people in the multi-front attack that began yesterday.
The dead included 85 civilians and 50 regime fighters, according to the monitor, which said today that IS had also kidnapped more than 400 civilians from captured territory.
He said they had been taken to areas under IS control in the west of Deir Ezzor province and to the border with Raqa province - the main IS stronghold in Syria - to the northwest.
The monitor said at least 42 IS fighters had been killed in the attack, adding that fighting was ongoing today, with regime forces backed by Russian air strikes trying to recapture lost ground.
It added that regime forces were bringing additional troops and military equipment from elsewhere in the city to the battlefront.
It denounced the deaths as a "massacre".
The IS assault puts the group in control of around 60 per cent of Deir Ezzor city, which is capital of the surrounding province of the same name, an oil-rich region that borders Iraq.
The jihadist group already controls most of the province, but regime forces have clung onto part of the city and a neighbouring air base despite repeated IS attacks.
If confirmed, the death toll in the assault would be one of the highest in a single attack by IS, though the jihadists have carried out mass murders before.
And in August 2014, the group massacred some 200 Syrian soldiers when it overran the Tabqa military base in Raqa province.
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