Police say the men, both aged in their 20s, were mixing chemicals in a container as friends and family looked on about 11pm when the explosion occurred at the house on Currawong Grove, Cannons Creek.

An Ambulance Victoria spokesman described the scene as horrific. Both men had to be placed into an induced coma at the scene because of critical injuries before being flown to Melbourne.

Advertisement: Story continues below It's believed a 24-year-old Pakenham man had both his legs blown off in the blast.

He also suffered blast injuries to his hands and burns to his face and airways and remains in a critical condition in the Royal Melbourne Hospital.

A 23-year-old Cannons Creek man suffered burns to his face, arms and airways and is in a critical condition in The Alfred hospital.

Paramedic Ben Meadley likened the injuries to those normally seen on battlefields.

"One (patient) had severe airway burns and the second patient suffered severe blast-type injuries, the type of injury you'd more liken to what you'd see in a war situation rather than in outer suburban Melbourne," he said.

The 24-year-old required a blood transfusion on the helicopter en route to hospital.

"Due to his severe blast injuries he'd lost quite a lot of blood ... we started by having to give him a blood transfusion," Mr Meadley said.

"We were able to give him quite a bit of blood and resuscitate his blood pressure. Then we were able to give him some powerful drugs and ... put him into an induced coma."

Police say the men were mixing the chemicals in their backyard in front of family and friends at the time of the explosion.

Neighbour Judy Gibbs said the explosion shook her house.

"I'd gone to bed and next minute there was this great, big, loud explosion - the windows in my house shook, the whole house shook," she told ABC radio.

Police said the arson squad would investigate the explosion.

- with AAP