More than 60 firefighters are tackling a major blaze at the Mackintosh Building in Glasgow.
Crews were called to the scene at 11.19pm on Friday, with 15 appliances in attendance.
A Scottish Fire and Rescue Service (SFRS) spokeswoman said they were not aware of any casualties.
It comes four years after fire ravaged the Glasgow School of Art building and a multi-million pound restoration project had been returning the famous art school to its former glory.
The May 2014 blaze came in the run-up to students' degree show, while graduation ceremonies had taken place on Friday.
Witness Aidan Dick said the fire and smoke grew in intensity "in the space of a few minutes" in the latest blaze.
He tweeted: "Glasgow School of Art is on fire again. Heartbreaking. My thoughts go to all students and staff, and I hope no one was caught in the blaze."
Scottish First Minister Nicola Sturgeon said she was heartbroken by the fire and paid tribute to the emergency services.
She tweeted: "This is clearly an extremely serious situation. My first thoughts tonight are for the safety of people - but my heart also breaks for Glasgow's beloved @GSofA.
"Once again, we are indebted to the bravery of our firefighters and other emergency services."
An SFRS spokeswoman said: "The Scottish Fire and Rescue Service is currently in attendance at a fire in the Mackintosh Building of The Glasgow School of Art.
"Operations control mobilised a number of fire engines to the scene after the call came in at 11.19pm on Friday, June 15.
"Firefighters are currently tackling the fire."
A number of roads have been closed while crews tackle the blaze.
Sauchiehall Street has been closed from Charing Cross to Rose Street, while Renfrew Street from Garnet Street to Cambridge Street has also been shut.
The building was designed by artist and architect Charles Rennie Mackintosh and built between 1897 and 1909.