Sgt Steve Armati of Wodonga police said at about 7.25pm two vehicles collided head-on after one car, headed to Wodonga, is believed to have crossed to the other side of the road and into the path of the second car that was headed towards Baranduda.

Sgt Armati said the first vehicle contained two adults and two children.

The driver, a Wodonga woman, 27, suffered a broken leg and was taken to Albury Hospital.

The man was a passenger and had been thrown from the vehicle as a result of the crash.

He remains in the intensive care unit at Royal Melbourne Hospital.

Sgt Armati said the second vehicle was driven by a Baranduda man, 36, who had two infants, aged six months and 18 months, as passengers.

The 18-month-old baby boy was flown to the Melbourne’s Royal Children’s Hospital with a broken clavicle and chest injuries.

Sgt Armati said the Baranduda driver of the second car was also taken to Albury Hospital with a broken sternum.

He said neither speed or alcohol were believed to have been factors in the collision, and road conditions were perfect.

Police were looking into whether seatbelts had been worn and why the first vehicle had crossed to the opposite side of the road.

Sgt Armati said more vehicles were on the region’s roads as people headed home from school holiday activities and with the arrival of the warmer weather, the end of the football season and the start of daylight savings this weekend.

"We are asking drivers not to be complacent but to be vigilant when they are out on the roads," he said.