Syrian regime forces battled Kurdish fighters in the eastern city of Hasakeh for the first time Saturday, leaving at least six people dead, a monitoring group said.
The Syrian Observatory for Human Rights said the fighting broke out at around 2 a.m. at several points in the city, control of which is split between the two sides.
Rami Abdel Rahman, director of the Britain-based group, said there had been heavy fighting since then.
Four regime forces and a Kurdish fighter had been killed so far, as well as a civilian woman killed by regime shelling of an area controlled by the Kurdish People's Protection Units (YPG).
The clashes began after Kurdish fighters detained around 10 regime forces they accused of seizing part of a demilitarized zone.
Under a deal agreed last year, Kurdish forces control around 30 percent of the city's Kurdish and mixed Kurdish-Arab districts, with regime forces controlling most of the city's majority-Arab districts.
Certain districts remain off-limits to both sides under the deal.
Against that backdrop, the two sides have fought jointly to push ISIS jihadists out of Hasakeh, but Kurdish relations with government forces are complicated.
The regime withdrew its forces from much of the country's Kurdish region in the north and northeast in 2012, focusing its attention on the burgeoning rebellion.
Since then, the Kurds have largely assumed security responsibility there and have worked to build autonomous local governments.
There has been an uneasy cooperation between the sides, both of whom view the Islamist rebel movement - including ISIS and Al Qaeda's Nusra Front - as a greater threat to them.
But there is no love lost between Syria's Kurdish population and the Assad regime. Bashar al-Assad and his father Hafez implemented a campaign of Arabization in Kurdish areas, which triggered bloody clashes including a brief uprising by Kurds in 2004 that was brutally quelled by the regime.
The Kurds are the largest nation without a state in the Middle East, and have been fighting on-and-off for autonomy from Syria, Iraq, Turkey and Iran - all of whom occupy parts of Kurdistan.
The Syrian civil war, as well as the collapse of the Iraqi military following ISIS's lightening advances last year, have seriously advanced the cause of Kurdish autonomy in those countries.
But cooperation between the Kurdish YPG militia and Syrian regime forces has allowed Hasakeh, a city of around 200,000, to remain relatively safe during the bloody Syrian civil war, despite efforts by ISIS to seize outlying areas.
More than 200,000 people have been killed in Syria since the beginning of the uprising in 2011.
AFP contributed to this report.