The committed drivers - Jenny and Lawrence Collins, Helen and Michael Collins, Colleen and Craig Willis, and Roz Thompson - have been passionately supporting cystic fibrosis for close two decades.

This year they are driving from Shepparton in Victoria down to Melbourne, catching the Spirit of Tasmania and travelling throughout the most southern state.

Collectively, the participants in the rally, who come from throughout Australia, raise between $350,000 and $500,000 annually for the incurable chronic illness.

Leeton group spokesman Mr Willis said the rally capped off a tough 10 months of fund-raising for the Leeton crew, which has raised $27,000 this year.

Mr Willis said the rally was a great deal of fun and a highlight of the year that everyone looked forward to.

"It's full of antics, there are a lot of costume nights (that are) sensational," he said. "There are all walks of life on the rally. The more you do the more you get out of it."

The 10-day journey will see the drivers travel to beautiful places including Hobart, Devenport and Port Arthur.

"It's a new adventure, I've never been to that part of the country so it will be great," Mr Willis said.

"We're absolutely stoked."

All funds go to the Cystic Fibrosis Registry to help find a cure. Mr Willis said the life expectancy of people living with cystic fibrosis had more than doubled from 16 years to 36 years since he first started rallying.

The significant improvement motivated the group to continue to support Cystic Fibrosis Australia in the hope that a cure would be found.

The group took off yesterday.