Russian air strikes and fierce clashes on Wednesday rocked a sliver of territory in southwestern Syria held by ISIS, a war monitor said.
Much of the southern province of Deraa had been quiet since Friday, when a ceasefire between rebels and Syria's regime ended a three-week government assault.
But a local branch of ISIS, known as Jaish Khaled bin Walid and based in a small area in Deraa's western countryside, was not included in the deal.
Early Wednesday, Russian warplanes began pounding the ISIS-controlled town of Saham Al Golan, according to the Syrian Observatory for Human Rights.
"Russian air strikes hit Saham Al Golan this morning, as dozens of shells and artillery fire hit the town," said Observatory founder Rami Abdel Rahman, from the UK.
In retaliation, ISIS launched an attack southward on Heet, a rebel-held town that recently agreed to return to regime control.
The Britain-based Observatory, which relies on a network of sources across Syria, gave no immediate death toll for Wednesday's fighting.
"Daesh [ISIS] stormed Heet, detonated a car bomb and advanced there and are also intensely bombing the nearby village of Zaizun," said Mr Abdel Rahman.
ISIS claimed responsibility on Tuesday for a suicide car bombing in Zaizun that left 14 fighters dead.
The claim, distributed through an online messaging service, included the first apparent reference to the south as an official ISIS "province", reflecting its plan to re-establish an Islamic "caliphate" despite its crushing military defeats in Syria and neighbouring Iraq.
Wednesday's clashes raged less than 10 kilometres from the armistice line with the Israeli-occupied Golan, and just 4km from Jordan.
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Anticipating an attack, thousands have fled the ISIS-held zone in recent days towards the Israeli-occupied Golan.
Up to 200,000 displaced people have already sought refuge near the sealed armistice line, according to the United Nations.
The strategic location makes the south a prize for President Bashar Al Assad.
Backed by Russia, his troops began an offensive on Deraa province on June 19 that killed dozens of civilians and displaced more than 320,000 people.
That ended Friday, when Moscow brokered a deal for rebels to surrender weapons and hand over towns to regime troops.
The agreement also provides for safe passage for thousands of opposition fighters and civilians to rebel territory further north, although those transfers have not yet begun.
The regime now controls around 80 per cent of Deraa province, while rebels hold around 15 per cent, according to the Observatory.
The rebel pocket includes parts of western Deraa and the surrounded southern districts of its provincial capital.
