An ambulance spokesman said the crash occurred 15 kilometres south of New Italy, near Ballina, just before 8am.

Two people died in one of the vehicles, Richard de Groot said. Their ages and gender are not known.

Two injured men, in their 20s, were taken to Lismore Base Hospital by helicopter with serious injuries, he said.

One man had head, neck and chest injuries and appeared to have concussion. The other had internal abdominal injuries. They are in a serious but stable condition, Mr de Groot said.

The Pacific Highway was closed for several hours between Maclean and Woodburn, a police spokesman said.