The Syrian Observatory for Human Rights said clashes in northwest Syria killed 22 regime fighters and militants on Sunday.
A truce since March 6 had largely stemmed fighting in Idlib after a months-long regime assault that killed hundreds of civilians and forced almost a million to flee.
The clashes in the Sahl al-Ghab area killed 15 regime fighters as well as seven militants including from Al-Qaeda-affiliated Hurras al-Deen group, the Britain-based monitor said.
"It's the highest death toll for fighters since the truce came into force," said Observatory chief Rami Abdel Rahman, who relies on sources inside Syria.
"There had been intermittent clashes and mutual bombardment between both sides before, but this is the most violent attack yet," he added.
According to AFP, the Idlib region of some three million people is dominated by the Hayat Tahrir al-Sham group led by Syria's former Al-Qaeda affiliate, but other militants such as Hurras al-Deen and rebel groups are also present.
The truce brokered by regime ally Russia and rebel backer Turkey has kept Syrian and Russian warplanes out of the region's skies, and largely held despite sporadic clashes or rocket fire.
Tens of thousands have returned to their hometowns, while hundreds of thousands of others remain in crowded displacement camps or in temporary shelters near the Turkish border.
