State television gave no word on any casualties from the attack that levelled the famed Carlton Citadel Hotel just across the road from the city's UNESCO-listed Citadel.
But the Syrian Observatory for Human Rights said there were dead and wounded among government troops occupying the building.
"The explosion that was heard in Aleppo's Old City was caused by explosives planted by Islamist battalions in a tunnel beneath the Carlton hotel, which was occupied by regime troops," the Britain-based monitoring group said.
State television said the hotel, which opened not long before the uprising erupted in March 2011 in a renovated 19th century hospital building, was completely flattened.
"Terrorists targeted the historic Carlton hotel in the Old City with a big explosion, destroying it completely and destroying several historic buildings nearby," the broadcaster said.
It was not the first time that rebel sappers had tried to blow up the hotel, whose location and ultra-modern facilities made it one of the city's most sought after before the war.
They carried out a similar attempt in February but the building escaped major damage.
A rebel offensive in July 2012 in which they seized large swathes of Aleppo left the historic Citadel and nearby hotels which had once thronged with foreign tourists on the front line of the deadly conflict.
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