A 36-year-old male has been fatally injured in a crash 80 kilometres south of Tennant Creek.
Initial investigations suggest a vehicle travelling north at speed struck a horse.
The Pajero subsequently rolled several times, the man was ejected from the vehicle, causing fatal injuries.
Three other male occupants survived the crash. One person was trapped in the vehicle and had to be cut from the wreckage by attending Fire and Rescue Officers.
They were transported to Tennant Creek Hospital by St John Ambulance.
Major Crash Detectives from Alice Springs attended and late this afternoon the highway was reopened to all traffic.
Investigations into the crash are ongoing.
Police continue to warn all travellers on the Stuart Highway to drive to conditions, your capabilities and those of your vehicle, avoid travelling at night if possible and always be on the lookout for wandering stock.