Available evidence that antihistamine-induced impairment of human psychomotor performance constitutes a traffic hazard is reviewed against a set of criteria which could theoretically be applied to any drug or group of drugs. Two distinct classes of histamine antagonists, which act at different receptors (H, and HJ are now available and they should be considered separately. H,-Antagonists are freely available to the public and are consumed in enormous quantities. They are a rather heterogenous group of drugs which share the common property of antagonising some of the effects of histamine. Other effects, particularly sedation. are prominent with many of the older members of the group and these drugs can be shown to impair performance in laboratory tasks and to interact additively with alcohol and other central nervous system depressant drugs. Despite this potential for impairment of driving ability, they are seldom suggested as causative factors in traffic crashes. This may, of course, be due to inadequacy of reportage. A number of new histamine H,-antagonists have been developed recently which only gain limited access to the central nervous system and appear to be less likely to cause impairment of performance skills. Histamine H,-antagonists have a much more restricted and closely supervised use in medicine and of the two agents currently available (cimetidine and ranitidine), only cimetidine appears to pose traffic safety problems largely because of Its ability to interfere with the metabolism of other drugs which depress the central nervous system. Appropriate prescribing should eliminate this problem. With both classes of histamine antagonist it is now possible for the prescriber to select from the available drugs one with a minimal potential for disrupting driving ability.