Police say it has been a horror start to the Rainbow Serpent Music Festival in western Victoria, with the first 24 hours of the five-day event being marred by a series of incidents.

A man in his 20s is in hospital after a suspected drug overdose and four people were injured when a truck rolled onto their tent late Thursday.

The man was rushed to hospital in a critical condition Friday morning.

Ballarat Superintendent Jenny Wilson said he was still in a very serious condition and it was a "tragic" situation.

"Having spoken to his mother this morning, she's devastated by the events," she said.

Police also arrested a man at the event for drug trafficking.

It is alleged the man, who has been remanded in custody, was selling ketamine, MDMA and other illicit drugs.

Three in hospital after truck rolls onto people in tent

The line at the Rainbow Serpent Festival on Thursday. ( ABC News )

At this stage police believe a truck that rolled onto four people in their tent late Thursday afternoon belonged to the festival's management, and was unregistered.

Two women and a man were seriously injured and are in a stable condition in hospital, after being run over in their tent.

Another man who was in the tent was treated at the scene for minor injuries.

"Certainly their lives have been impacted by this event," Superintendent Wilson said.

Police said there was no-one in the truck at the time.

"My understanding is that it's part of the festival management's normal fleet of trucks," Superintendent Wilson said.

The ABC has contacted the festival's management to confirm whether the truck belonged to them but has not received a response.

After the incident, festival organisers released a statement saying staff were devastated by the event.

They said emergency services on site had responded immediately and procedures were followed.

Police are seeking witnesses to the incident.

Young woman killed in car accident on her way to the festival

A 19-year-old Yarraville woman who died in a car accident on the Western Freeway at Gordon on Thursday was on her way to the festival with her friend.

The driver of the car, an 18-year-old woman from Aspendale, was taken to hospital with serious lower leg injuries.

Police believe the car the women were travelling in hit a safety barrier and rolled several times.

"Those two young ladies had been friends most of their lives, and that's a significant impact not only on their families but on us as a community," Superintendent Wilson said.

"Police are really disheartened this morning [that] we've had such tragedy at the event."

Police urge people not to take risks

The festival has been running for 22 years and in the past few years there have been concerns over issues including drug overdoses and sexual assaults.

Two people have died of drug overdoses at the festival in the past seven years, and there have been more than a dozen drug-related hospitalisations.

Three allegations of sexual assault at the event have been made to police in the past five years.

Police say they want people to have a good time at the festival, without taking risks. ( Supplied )

Superintendent Wilson urged people to rethink the activities they were going to engage in at the festival.

"Our message is we want everyone to come and have a good time, but we ask them not to take illicit drugs because we don't know what reaction … they will have," she said.

"No-one knows what those drugs contain except the criminals that made them.

"[I feel] sadness and disappointment … knowing that so many young people won't reach their full potential.

"There are many families and parents who are impacted at the moment."