The study was done to check replication of changes in sensitivity with a simple simulator as had been obtained in an experiment using the real road situation. Another purpose was to control simulator sickness which could have confounded data from testing with a simulator or in actual driving. Sensitivity of the drivers (72 healthy young adults, M age = 24 yr., SD = 5) while performing the driving task was measured in terms of subjective ratings of simulator sickness and affect, and physiological measures (i.e., galvanic skin responses and skin temperature) at different driving speeds and in driving mode conditions, using a simple vehicle simulator. Analysis showed measures of drivers’ state, including simulator sickness, physiological indices, and subjective reports, increased with driving speed (30→90→120 km/hr.) and driving mode change from the regular speed to sudden increasing to sudden decreasing speeds. Particularly, the results suggest that the increased autonomic nervous activation induces increase of rated simulator sickness. Based upon the same tendency in change of the simulator sickness and physiological state with driving speed and driving mode conditions, it was concluded that, if the results obtained from the simulator experiment can be generalized to the real situation, the simulator sickness must be considered a confounding factor. The results also suggest that the changes in human sensitivity are dependent upon aspects related to speed of a vehicle and driving mode.