Police forensics and NSW Fire and Rescue are investigating the blaze that gutted the former female ward 15 on Saturday afternoon.

Police are treating the fire - which took five hours to extinguish - as suspicious but are also exploring the possibility of an electrical fault.

On Monday morning, police called for public help with their investigation, asking anyone with information or dashcam or CCTV footage from the area to come forward.

The building, believed to have been constructed between 1897 and 1899, was one of many in the historic state significant site. Up to 50 personnel from NSW Fire and Rescue and RFS battled the blaze, which was notified at 4.25pm.

On Sunday, investigators launched a drone to capture vision of the damaged interior.

NSW Fire and Rescue inspector Chris Hughes said almost all the floors and roof of the two-storey structure had been destroyed, as was an attic. Slate roof tiles, twisted iron and burnt bricks were scattered throughout. Timber beams and other structures were still falling on Sunday morning, posing access and safety issues for firefighters.

They had stayed there overnight, dousing flare-ups, though the fire proper was mostly extinguished by 9pm.

"It's likely that it will have to be demolished because there are cracks throughout the [support] columns, brickwork and chimneys and over time that will worsen," Inspector Hughes said.

"But a developer may say there are parts they can save."

He was confident the blaze had started in the roof, based on personnel's early photos at the scene. They had to adopt defensive firefighting tactics due to the structural dangers.

On Sunday, the authority's Fire Investigation Research Unit deployed a sniffer dog to detect whether any ignitable fuels were on the site. Nearby residents reported an explosive sound around the time of the outbreak but Inspector Hughes said this could have been any number of things.

Old timbers and slate tiles holding in the heat made firefighting challenging.

Detective Senior Constable Tom Pollock said two NSW Fire and Rescue investigators and a police crime scene officer were probing the cause.

"We still have to determine the point of origin and the cause," he said on Sunday morning.

"It is still smouldering so access is an issue and it limits what we can do," he said.

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While the blaze was being treated as suspicious at this stage, investigators were not ruling out an electrical fault. Essential Energy had to disconnect electricity on Saturday after firefighters arrived.

DSC Pollock said police were concerned about ongoing vandalism and intruders at the site and could not discount that it was deliberately lit.

He has also spoken to Ben Xiao, the owner's son, about the fire. DSC Pollock said he intended to speak to him again about trespassers on the property.

Police also have to determine the building's value. Anything over $500,000 must be notified to the NSW Coroner.

The former female ward once housed between 80 and 100 patients. It was later used as part of Strathallen for developmental disability services but has been vacant for some time.

Firefighters were fortunately able to prevent the blaze's spread to nearby ward 16, built during the same period.

The state government declared the entire Kenmore Hospital site state significant in 2005. It was sold by the state government to Longreach Capital Pty Ltd for $3 million around the same time but was later on sold to LAJC Energy Pty Ltd and again in 2015 to Australia China International Holdings Pty.