The Islamic State of Iraq and the Levant (ISIS) launched an attack on Thursday against its Al-Qaeda rival, the Al-Nusra Front, and its local Syria allies, AFP reported.
The attack, in a town on the Iraqi border, killed dozens of fighters, according to activists who spoke to the news agency.
The clashes centered on Al-Bukamal, from which ISIS was expelled earlier this year. Observers said the Al-Qaeda splinter group was trying to regain a presence in the border town in a bid to bolster its supply lines stretching into Iraq, where it has been engaged in a campaign against Iraqi government forces.
The Britain-based Syrian Observatory for Human Rights, an anti-regime activist group, told AFP that at least 51 jihadist and Islamist fighters were killed, with 39 of the fatalities coming from the ranks of the Al-Nusra Front and its allies.
ISIS fighters were seeking to link up with their comrades over the border in Iraq, said Rami Abdel-Rahman, the head of the Observatory.
Local activists said the clashes continued throughout the day as the Al-Nusra Front and its allies, the Qadisiya Brigade and the Omar al-Mukhtar Brigade, launched a counterattack.
The border crossing itself on Syria’s side remained in the hands of the mainstream rebel Free Syrian Army, according to AFP.
Al-Bukamal has been under the control of fighters opposed to the Damascus regime since November 2012, but Al-Nusra and its allies forced out ISIS fighters in heavy fighting earlier this year.
Powerful jihadist rebel groups in Syria, including the Islamic Front and the Al-Nusra Front, have been locked in fierce fighting with ISIS since January.
The fighting broke out after allegations that ISIS brutally abused civilians and other opposition fighters battling to topple the regime of Syrian President Bashar Al-Assad.
Tensions were further exacerbated when Al-Nusra and other rebel factions accused ISIS of killing Islamist Front commander Abu Khaled al-Suri in a suicide car bomb attack in February.
Last week, Al-Qaeda chief Ayman al-Zawahiri told the fighting jihadists to accept independent Islamic arbitration to end the infighting, saying in an audio message the violence is "sedition".