The authors present a case report of a cocaine abuser who developed ac
ute hepatitis and an extrapyramidal reaction after administration of c
lozapine, a novel dopamine antagonist. Previous clinical experience wi
th clozapine is reviewed. Both clozapine and cocaine undergo hepatic m
etabolism, increasing the potential for hepatotoxicity in selected pat
ients. The authors also review hepatic metabolism of biogenic amines,
their central nervous system effects, and the pharmacologic effects of
clozapine and other abused substances on bioamine metabolism. Substan
ce abusers' high susceptibility to hepatotoxicity highlights the need
for careful monitoring for this form of liver dysfunction when adminis
tering clozapine.