OBJECTIVE: The authors added haloperidol, a potent D2 blocker, to ongoing treatment with clozapine in patients with schizophrenia to determine the effects of this combination on dopamine D2 receptor blockade, prolactin level, and extrapyramidal side effects. METHOD: At baseline and 4–8 weeks after the addition of haloperidol (4 mg/day) to ongoing clozapine treatment, five patients were examined for prolactin elevation, extrapyramidal side effects, drug plasma levels, and D2 receptor occupancy measured with [11C]raclopride and positron emission tomography imaging. RESULTS: Adding haloperidol significantly increased D2 receptor occupancy, from a mean of 55% to 79%, and significantly increased the prolactin level. One patient developed akathisia, and another manifested mild extrapyramidal side effects. CONCLUSIONS: Adding a modest dose of haloperidol to clozapine results in the high D2 receptor occupancy and sustained prolactin elevation usually associated with typical antipsychotics. These findings suggest that the lack of prolactin elevation associated with clozapine derives mainly from low D2 receptor occupancy and not from the medication’s effects on other receptors.