Nick Mongta, 22, Joshua Taylor, 19, Corey Bray, 28, and Chris Reddin, 22, died when their car became airborne, ploughed into a tree and bent in two off the highway near the small town of Pyalong, north of Melbourne.

One of the four friends survived for at least 15 minutes, holding the hand of a local female police officer, before dying.

Police confirmed a canister containing a small amount of white substance, as well as drug paraphernalia, was found in the wreckage. The substance will be forensically tested.

Investigators are yet to officially identify who was behind the wheel. A red P-plate was also found at the scene of the crash.

It is believed at least one of the men was previously known to police.

The men were from Echuca, Moama and Craigieburn.

Mr Reddin, who leaves behind a baby boy, was remembered by grieving relatives as a "beautiful person".

"He was always so good to me, and always so loving to everyone," relative Jayden Reddin said.

"There are a lot of people who are extremely sad today ... crying and devastated," he said. "This is something we will have to try and get through together."

Another relative of one of the victims, who requested not to be named, said Mr Reddin, Mr Taylor and Mr Mongta were former students of Echuca College, who were outgoing, charismatic and "loved hanging out with their mates".

It is understood their silver 2001 Holden V8 SS Commodore hit a wire rope barrier, rolled and then slammed into the tree off the highway near Halpin Court.

The impact of the crash bent the car in two.

Speaking at the site of the crash on Wednesday, road policing assistant commissioner Robert Hill said the "horrific" scene was one of the worst he had encountered in his years in the field.

"It is a shocking sight, it is a shocking scene ... it is something that certainly will stay with me for some time," he said.

Mr Hill said initial investigations indicated that the car was travelling north when the driver failed to negotiate a left bend in the road about 6.30am.

"For one reason or another that vehicle has careened to the right-hand side and travelled off the road ... has struck a wire road barrier, or the commencement of a wire rope barrier, has then travelled airborne some distance and then has crashed into a tree after rolling," he said.

"The roof of the vehicle has actually struck the tree."

No one saw the crash, but some people have reported hearing it unfold to police.

"We're looking at usual factors that include fatigue, alcohol, or drugs, that would have caused this crash," Mr Hill said on Wednesday.

He was in the same part of the state 12 months ago, after four other people were killed in tragic circumstances.

"Yet again we've seen four people lose their lives in circumstances that could have been avoided," he said.

"We have four families now that will be grieving, grieving today, tomorrow and for their lifetime."

Halpin Court resident Rosa Bazzano said her neighbour, who was new to the area, had happened upon the crash scene on her way to work.

"She's the one who rang triple-0," she said.

Detectives from the Major Collision Investigation Unit are investigating.

A section of the Northern Highway surrounding the crash was closed for several hours, but reopened shortly after 5.30pm on Wednesday.

- with Alana Schetzer, Nick Toscano, Rania Spooner