Emergency services were called to the scene near Cassilis around 10am after reports a westbound SUV and eastbound Landcruiser had collided.

Despite the efforts of paramedics and the Westpac Rescue Helicopter's critical care medical team to treat the driver and sole occupant of the Hyundai SUV, she died at the scene.

The driver and sole occupant of the Landcruiser - a 63-year-old man - was flown to John Hunter Hospital in a stable condition, suffering back injuries.

Drivers were urged to delay journeys as the road was closed in both directions for hours as police and emergency services worked to clear the scene. The Golden Highway re-opened around 6.30pm.

Officers attached to Hunter Valley Police District attended and established a crime scene, which will be forensically examined, police said. A report will be prepared for the Coroner.

As inquiries into the incident continue, police are appealing for anyone with information to contact Crime Stoppers on 1800 333 000.

Meanwhile, in a separate incident, the Westpac Rescue Helicopter was tasked to reports of a quad-bike crash on the Stockton sand dunes Saturday afternoon.

A spokesperson for the services said, owing to access issues, the helicopter's critical care medical team had to be winched to a 42-year-old man who had sustained pelvic injuries as a result of the accident. He was extricated in a basket stretcher and flown to John Hunter Hospital for treatment in a stable condition.