Sedative side effects of antihistamines have been recognized to be potentially dangerous in car driving, but the mechanism underlying these effects has not yet been elucidated. The aim of the present study is to examine regional cerebral blood flow (rCBF) responses during a simulated cardriving task following oral administration of dchlorpheniramine using positron emission tomography (PET) and [15O]H2O. Healthy volunteers drove a car in a simulated environment following oral administration of a sedative antihistamine, d-chlorpheniramine, or placebo. Their rCBF was measured in the conditions of resting, active driving, and passive driving. Performance evaluation revealed that the number of lane deviations significantly increased in the dchlorpheniramine condition (p<0.01). Subjective sleepiness was not significantly different between the two drug conditions. The regions of diminished brain responses were detected following d-chlorpheniramine treatment in the parietal, temporal and visual cortices and in the cerebellum. These results suggest that d-chlorpheniramine tends to suppress visuo-spatial cognition and visuo-motor coordination even when the subjects do not recognize subjective feeling of sedation.