To investigate the effects of 12 weeks of clozapine treatment on levels of cholesterol and related lipids in patients with schizophrenia. Prospective study. University department associated with a teaching hospital. Eight patients (6 women and 2 men) with a clinical diagnosis of schizophrenia consistent with DSM-IV criteria. The patients were classified as treatment-resistant and had not responded to treatment with at least 2 conventional antipsychotics. Current antipsychotic medications were tapered and treatment with clozapine was initiated. Cholesterol and serum lipid levels, as well as Brief Psychiatric Rating Scale (BPRS) scores were measured before and after 12 weeks of treatment with clozapine. Clozapine treatment significantly improved the BPRS scores but did not significantly alter serum lipid levels, except triglyceride levels, which increased. The previously reported lower levels of cholesterol in treatment-resistant patients with schizophrenia cannot be attributed to the effects of clozapine administration. Further research is required to support and clarify the effects of antipsychotic drugs on lipid levels.