Update 1pm Tuesday
Inspector John Sheehan said the ACT woman airlifted from Monday's crash near Marulan had been taken to Canberra Hospital.
She had also suffered a fractured pelvis and ribs in the collision.
Police are awaiting blood test results for the male driver of the Toyota. No charges have been laid in regard to the crash.
Meantime, Hume Police, as distinct from Highway Patrol, had undertaken 2783 random breath tests, issued six infringement notices for offences such as not wearing a seatbelt and recorded five drink-driving offences, across the weekend.
Police conducted Operation Go-Slow from midnight Friday to midnight Monday.
Acting operations inspector Keith Price said driver behaviour had been generally good.
Update 3.34pm Monday
Police say the female passenger in the Toyota, an ACT woman aged in in her late twenties, suffered serious head injuries and was airlifted to hospital.
The male driver of the Toyota did not sustain any physical injuries and was taken to hospital under police guard for mandatory testing.
The male driver of the Hyundai suffered serious leg injuries and his male and female passengers suffered minor injuries.
A woman has been airlifted to hospital and three others injured following a crash north of Marulan.
Hume Police District senior constable Adam Churchill said a silver Toyota Corolla was travelling at the rear of a maroon Hyundai i30 when it collided with the back of the car. The crash occurred about 1km south of the Highland Way turnoff on the Hume Highway's southbound lane.
Both cars careered from the highway down an embankment in the median strip.
Both vehicles crashed into trees and sustained significant front-end damage.
The driver of the Toyota Corolla is a 38-year-old man with a female passenger in her late 20s, both from the ACT.
The woman has been airlifted to hospital by the TOLL Rescue Helicopter service.
The man was taken to Goulburn Base Hospital by road ambulance.
NSW Police Rescue was required to cut open the door of the Toyota Corolla to free the woman.
A 24-year-old ACT man in the Hyundai i30 suffered a broken foot and ankle and was conveyed by road ambulance to Goulburn. His male and female passengers were out of the vehicle and talking to police but were also taken to Goulburn Base Hospital as a precaution.
Traffic was banked up for many kilometres on highway's northbound lane. It also remained heavy in the southbound lane at Carrick, where vehicles were lined up to turn right into Carrick Road.
Motorists are advised to allow extra travel time..
Traffic remains heavy on the Hume Highway at Marulan after a two-vehicle crash.
A Transport Management Centre spokeswoman said one of two northbound lanes was closed for emergency services.
The crash has also affected southbound traffic on the highway.
A helicopter is currently en-route to the nearby heavy vehicle safety station.
The Crash Investigation Unit, emergency services and Transport for NSW crews are at the scene.
Motorists are advised to expect significant delays and exercise caution.
A motor vehicle accident has slowed down traffic in both directions of the Hume Highway in Marulan.
At about midday on Monday, October 7, the RFS were notified of the accident near Highland Way.
NSW RFS Southern Tablelands Zone operational officer Lachlan Gilchrist said crews were on top of things.
"Crews from the Marulan Rural Fire Brigade are on scene at the moment."
"They are focusing on providing fire protection."
Ambulance is also at the scene treating the patients.
The highway remains open.
More to come.
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