An explosion at a chemical works on an industrial estate sent a fireball 40ft into the air, a witness told the BBC.
"There was a huge bang, the whole building rattled and we saw flames shoot 40ft as a cloud swept up," said Chris Ball, who works next to the site in Andoversford, Gloucestershire.
At its height 100 firefighters and 20 fire engines tackled the blaze at the Biolab plant near Cheltenham.
Police said there were at least three explosions after the fire broke out.
No evacuation plans
Biolab specialises in the treatment of swimming pool and spa water.
A Gloucestershire Police helicopter was called to help with the fire, and provided thermal imaging pictures to firefighters as well as enabling the police to broadcast loud-speaker messages to the public, passing on safety advice.
Map of Andoversford
Sections of both the A40 and A436 remain closed
There have been no reported casualties, but residents in the immediate vicinity as well as in the Northleach, Bourton and Stow areas were asked to stay indoors and keep their doors and windows shut.
"The explosions made the building vibrate like a very heavy thunder storm," said Simon Pratt, who works for R & R Catering Hire, which backs onto Biolab.
"The building was totally ablaze and uncontrollable within just a few minutes," he added.
The A40 remains closed between Frogmill and Station Hill, and the A436 is closed between the Hampnett turning and the clockhouse cross roads.
A major chemical fire has started at an industrial estate at Andoversford near Cheltenham in Gloucestershire.
Police said there had been at least three explosions at the Biolab plant, which specialises in the treatment of swimming pool and spa water.
Nearby businesses have been evacuated and witnesses told BBC News that thick black smoke is enveloping the area.
Police have closed a section of the A40 which passes the estate and the A436 to Stow-on-the-Wold.
Local residents have been advised to keep doors and windows closed as a precautionary measure.
'Mushroom cloud'
Assistant Divisional Fire Officer Dave Hornibrook said: "At the moment, our efforts are to minimise the impact of the smoke given off, as we believe there are toxins in it.
"The police helicopter is warning residents to keep their windows shut."
Map of Andoversford
The smoke from the fire is spreading across a large area
Terry Britchford, who was working in a barn opposite the industrial estate, said: "The building made a rumbling sound and at first I thought it was very loud thunder.
"My friends and I then ran across the field towards where [the smoke] was coming from, thinking it may be a plane crash at that time.
"We could then see the fire and smoke coming from the industrial estate. It was a massive mushroom cloud filling the sky."
i dont like hearing about that kind of stuff...i get scared that it will happen at Alans work 
