At a meeting in Moscow, the presidents of Turkey and Russia expressed "serious concern" over the violence in Idlib province.
Russia-backed regime fighters have for weeks been chipping away at the edges of the jihadist stronghold, which borders Turkey, after bombarding it for months.
But hardline rebels and jihadists on Tuesday attacked loyalist positions in the south of the bastion, the Britain-based Syrian Observatory for Human Rights said.
"Violent clashes east of the town of Khan Sheikhun broke out at dawn after jihadist and opposition groups attacked regime positions," Observatory chief Rami Abdel Rahman said.
The attack was led by the Al-Qaeda-linked Hurras al-Deen group and another jihadist faction, Ansar al-Deen, he said.
The clashes killed at least 29 regime forces and 31 rebels and jihadists, the Observatory said in an updated death toll, before government troops repelled the jihadists.
In the southeast of the bastion, eight rebels were killed trying to sneak through frontlines towards regime positions near the Abu Duhur military airport, the monitor added.
Elsewhere in southern Idlib, 10 civilians, among them a child, were killed in regime air strikes, the Observatory said.
Regime forces recaptured Khan Sheikhun last week, and have been massing north of the town in recent days.
The town lies on a key highway running through Idlib province, and fully recapturing the artery would allow the government to reconnect Damascus to second city Aleppo.
Heavy regime and Russian bombardment has hit areas north of Khan Sheikhun in recent days, in the vicinity of the town of Maaret al-Noman, the next stop north on the highway.
'Serious concern'
On Monday, regime and Russian air strikes killed 12 civilians in the jihadist stronghold, the Observatory reported.
"The situation in the Idlib de-escalation zone is of serious concern to us and our Turkish partners," Russian President Vladimir Putin said at a press conference with Turkish counterpart Recep Tayyip Erdogan.
He said Turkey had "legitimate interests" to protect on its southern borders and supported the creation of a security zone in the area.
Putin said he and Erdogan had agreed "additional joint steps" to "normalise" the situation in Idlib, but did not provide details.
The Idlib offensive comes despite a deal signed in September last year by Moscow and rebel backer Ankara to avert a full-blown assault on the Idlib region which hosts some three million people.
The presidents of both countries were set to meet in Moscow on Tuesday.
Hayat Tahrir al-Sham - a group led by Syria's former al-Qaeda affiliate - extended its administrative control over the whole of Idlib in January, but other rebel factions remain present.
A spike in bombardment since late April has killed more than 920 civilians, the Observatory says. The United Nations says it has caused more than 400,000 people to flee their homes.
The Syrian civil war has killed more than 370,000 people and displaced millions since starting in 2011 with the brutal repression of anti-government protests.
Follow us on Twitter: @The_NewArab
Follow the Middle East's top stories in English at The New Arab on Google News
