The pharmacokinetics and pharmacodynamics of chlorpromazine, haloperidol, clozapine, and risperidone are described. Most traditional antipsychotic drugs have similar pharmacokinetic profiles that differ from the newer agents in several key respects. Traditional agents tend to be completely absorbed and undergo extensive presystemic elimination, but clearance tends to be almost exclusively by hepatic-enzyme metabolism. The volume of distribution is large, steady-state plasma concentrations are highly variable, and many traditional antipsychotic drugs have pharmacologically active metabolites. The newer antipsychotic agents clozapine and risperidone are also well absorbed and undergo extensive presystemic elimination. They are cleared mostly through hepatic-enzyme metabolism, but a small portion of risperidone is cleared renally. Steady-state plasma concentrations of clozapine and risperidone exhibit large interpatient differences at therapeutic dosages. The primary metabolite of risperidone, 9-hydroxyrisperidone, has activity equipotent to that of the parent drug. It is not clear whether clozapine produces active metabolites. Basic information on the pharmacokinetics and pharmacodynamics of clozapine and risperidone is known; however, more information is needed.