Despite the extremely widespread use of antipsychotic medications, there is little evidence from the surveys conducted to date, that this class of psychoactive medications is significantly implicated in vehicular crashes or deaths. In five major surveys of vehicular fatalities, in which drug and alcohol analyses were obtained, only two of over 800 victims studied involved detection of antipsychotic medications. It is clear that the acute administration of antipsychotics in normal individuals does induce sedation and performance decrements in visual-motor coordination and specific attentional behaviors, which have a deleterious effect on driving behavior. On the other hand, it should be emphasized that antipsychotics are rarely used on an acute basis and tolerance to the sedation and decreased alertness does occur during chronic treatment. Antipsychotic drugs have the capacity to potentiate the effects of alcohol, sedative hypnotics, narcotics and antihistamines; therefore, the combination of antipsychotics with these substances increases the impairment of driving behavior. There is an indication that the less sedating piperazine phenothiazines and the butyrophenones may have little or no effect on psychomotor performance, and antipsychotic drugs of these two subclasses may have a distinct advantage, at least in terms of driving performance, over the other more sedating drugs. Antipsychotic drugs are almost never used for recreational or abuse purposes; therefore, more central to the focus of this review is the effect that antipsychotics may have on the driving behavior of those seriously disordered mentally ill patients who require continued maintenance on these medications. There is good agreement in the literature which suggests that schizophrenic patients demonstrate improved psychomotor performance during chronic treatment with antipsychotic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)