Shocking pictures from the scene show Ayr Station Hotel up in flames as firefighters tackle the enormous fire.
Crews battled overnight to control the flames which ripped through the spire of the derelict old building in the town centre.
The alarm was sounded at around 5.30pm on Monday night (September 25), with the inferno raging into the early hours of Tuesday morning.
Local photographer Robert Collie said: "Last night it was pandemonium. They have shut down all the roads. It's still smouldering this morning."
Thirteen fire appliances were sent to the scene, the Scottish Fire and Rescue Service said. There were no reports of injuries.
Two teenagers, aged 13 and 17, have been arrested and charged in connection with the incident, Police Scotland said.
The blaze has caused major disruption in the town, with a number of road closures in place.
Due to the hotel's proximity to Ayr railway station, many trains have been cancelled. Scotrail said on Tuesday morning (September 26) the line remains between Ayr and Girvan and between Ayr and Irvine.
Bus replacement services have been put in place for rail passengers.
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