Rebels seized control of most of Idlib province early in the three and a half year old civil war but troops have held out in the provincial capital, resupplied by air.
Fighters of Al-Qaeda affiliate Al-Nusra Front and Islamist rebel units attacked the city from all sides, the Syrian Observatory for Human Rights said.
"Since dawn, fierce fighting has raged at army checkpoints all around Idlib city," said the Britain-based monitoring group, which has a wide network of sources inside Syria.
At least five rebel fighters were killed, the Observatory said, adding that it had no immediate word on any army losses.
Rebels made a previous attempt to take the city earlier this year but Monday's assault was "unprecedented, the biggest since the beginning of the revolt" in 2011, Observatory director Rami Abdel Rahman told AFP.
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Abdel Rahman said that the rebels had activated sleeper cells inside Idlib to launch attacks on the army behind its lines.
He said policemen who sympathised with the rebels joined the insurgents in a brazen attack on a key official building in the city.
"Policemen backed by sleeper cell members of Al-Nusra, already inside the city, attacked the governorate building but they were quickly pushed back out by regime forces," said Abdel Rahman.
Before the Syria war broke out, the city of Idlib was home to 165,000 people but the population has increased with the arrival of hundreds of thousands of displaced people from other parts of the country.
Idlib province lies on the border with Turkey and has long been one of the rebels' principal supply routes.
As a result, rebel fighters in the province are generally better armed and equipped than their counterparts elsewhere in Syria. who have suffered a series of setbacks at the hands of the regime this year.