A Beechcraft 200 Super King Air, VH-SKC, departed Perth Airport, WA (PER) at 10:09 UTC on a charter flight to Leonora Airport, WA (LNO) with one pilot and seven passengers on board. Until 10:32 the operation of the aircraft and the communications with the pilot appeared normal. However, shortly after the aircraft had climbed through its assigned altitude, the pilot’s speech became significantly impaired and he appeared unable to respond to ATS instructions. Open microphone transmissions over the next 8-minutes revealed the progressive deterioration of the pilot towards unconsciousness and the absence of any sounds of passenger activity in the aircraft. No human response of any kind was detected for the remainder of the flight. Five hours after taking off from Perth, the aircraft impacted the ground near Burketown, Queensland, and was destroyed. There were no survivors. The aircraft’s flightpath was consistent with the aircraft being controlled by the autopilot with no human intervention after the aircraft passed position DEBRA. After the aircraft climbed above the assigned altitude of FL250, the speech and breathing patterns of the pilot displayed changes that were consistent with hypoxia, but a rapid or explosive aircraft cabin depressurisation was unlikely to have occurred. Testing revealed that Carbon Monoxide and Hydrogen Cyanide were highly unlikely to have been factors in the occurrence, and the absence of irritation in the airways of the occupants indicated that a fire in the cabin was also unlikely. The possibility of the pilot alone being incapacitated by a medical condition such as a stroke or heart attack would appear unlikely, given that there was no apparent activity or action by the other occupants of the aircraft for the duration of the flight. The investigation concluded that while there are several possible reasons for the pilot and passengers being incapacitated, the incapacitation was probably a result of hypobaric hypoxia due to the aircraft being fully or partially unpressurised and their not receiving supplemental oxygen. Due to the extensive nature of the damage to the aircraft caused by the impact with the ground, and because no recording systems were installed in the aircraft (nor were they required to be), the investigation could not determine the reason for the aircraft being unpressurised, or why the pilot and passengers did not receive supplemental oxygen. SIGNIFICANT FACTORS: 1. The aircraft was probably unpressurised for a significant part of its climb and cruise for undetermined reasons. 2. The pilot and passengers were incapacitated, probably due to hypobaric hypoxia, because of the high cabin altitude and their not receiving supplemental oxygen.