Large explosions have rocked a fuel depot near Hemel Hempstead in Hertfordshire shooting flames hundreds of feet into the sky.
Police say there are 39 casualties, with two people seriously hurt.
The first blast happened at 0603 GMT at the Buncefield fuel depot, close to junction 8 of the M1 motorway and was heard as far away as the Netherlands.
The fire, which police believe was caused by an accident, could last days with more explosions expected.
The area around the site has been evacuated, while police have advised residents living nearby to keep their windows and doors closed because of fumes.
Thick clouds of smoke are spreading to the south-east and south-west, but are not thought to be toxic.
Earlier rumours a plane was involved in the incident were unfounded, said a police spokesman.
Witnesses said another two explosions followed the first at 0626 GMT and 0627 GMT.
In total, 20 petrol tanks are involved in the fire, each said to hold three million gallons of fuel.
Hertfordshire's chief fire officer Roy Wilsher said it was the largest fire he had ever witnessed.
"I think you need to go back into the history of Milford Haven and areas like that to see this sort of fire scale," he said.
Tanker driver Paul Turner said he ran for his life after the explosion lifted him off his feet.
"I just saw this great big ball of fire come up from behind the building. It was about 50 metres wide," he told the BBC.
"Then there was the loudest explosion I have ever heard in my life. I got up, turned around and ran to my car and sped out of there as fast as I could."
The M1 has been closed both ways between junctions 6a and 12 and is expected to stay shut for the rest of the day.
The M10 motorway is closed in both directions between junction 1 and junction 7 as well as some arterial roads in Hemel Hempstead.
Motorists have been told not to go "anywhere near the M1 from the M25 upwards".
At Heathrow airport some flights were forced to delay landing because of smoke, but Luton airport was said to be operating as usual.
Many houses have been damaged, with some reporting feeling effects from the explosion as far away as Oxfordshire - while it was heard in a number of counties and even France and the Netherlands.
Eye-witnesses reported buckled front doors, cracked walls and blown-out windows.
The Buncefield depot is a major distribution terminal operated by Total and part-owned by Texaco, storing oil, petrol as well as kerosene which supplies airports across the region, including Heathrow and Luton.
The country's fifth largest fuel distribution depot, it is also used by BP, Shell and British Pipeline.
Police said there was no indication the explosion would cause fuel shortages and warned against panic-buying.
"We strongly advise against this as recent events have shown that panic buying alone can cause fuel shortages," said Hertfordshire Police Chief Constable Frank Whiteley.
A spokesman for Total said: "We are doing everything we can to support the emergency services and to bring the situation under control."
Concerned relatives can call a police casualty bureau on 0800 096 0095, or from abroad on 0207 1580125.
