A double blind cross-over study was performed to compare the sensitivity of "oof road" driving with that of laboratory tests of driving-related skills to drug induced sedation. Twelve experienced drivers (6 M, 6 F) received single oral doses of the H1-antagonist diphenhydramine 25, 50 and 100 mg and placebo. Each treatment was administered on 2 separate occasions, once in the driving school when real driving skills were assessed and again in the laboratory when performance of an adaptive tracking task, body sway and visual reaction were measured. On all occasions subjects assessed their own performance and alertness/sedation using visual analogue scales. Data were subjected to analysis of variance and differences assessed by Newman Keul's test. Diphenhydramine failed to impair driving performance at any dose while all doses produced significant changes in each of the 3 laboratory tests. Subjects rated themselves sedated after all 3 doses of active drug in the laboratory but only after the 100 mg dose in the driving school. Tests performed in the psychopharmacology laboratory appear to be more sensitive to the sedative effects of diphenhydramine than tests of "off road" driving. The implications are discussed.