Two studies of real-life driving are reported in which individual differences in fatigue and stress were explored in Australian professional and non-professional drivers. In Study 1 58 truck drivers completed subjective measures of mood and stress states before and after a prolonged driving trip. The Task-Induced Fatigue Scale (TIFS) was also used to assess fatigue before and after driving. The Driver Stress Inventory Fatigue Proneness Scale was completed before the driving trip to assess individual differences in fatigue. In Study 2 104 non-professional drivers completed the same subjective state measures before and after a short-duration drive, as drivers in Study 1. Drivers also completed the Fatigue Proneness Scale. Fatigue-prone drivers in both studies showed elevated levels of state fatigue, tension, unpleasant mood and task-related cognitive interference. The results suggest that high Fatigue Proneness drivers may be at risk from fatigue during both prolonged and relatively short driving trips.