This study will examine the physical response to clozapine or chlorpromazine in people with schizophrenia that has not improved with treatment.

This is a longitudinal double-blind 12-week study of the clinical and biochemical response to clozapine or chlorpromazine in a group of treatment-refractory schizophrenic patients.

The study has 4 phases: (1) A recruitment period; (2) a period of discontinuation of psychotropic medication; (3) a drug-washout period; and (4) a 12-week double-blind trial of clozapine or chlorpromazine.

Inclusion Criteria:

• 19-60 years of age
• Diagnosis of schizophrenia
• BPRS score > 50
• Clinical Global Impressions rating > 4
• One of the following: BPRS items rated greater than or equal to 4, conceptual disorganization, suspiciousness, hallucinations, unusual thought content.
• At least 2 six-week trials of different neuroleptics given at a dosage equivalent to at least 600 mg per day of chlorpromazine OR at least 1 eight-week trial of a neuroleptic given at a dosage equivalent to at least 800 mg per day of chlorpromazine.
• The patient (or the patient's authorized legal representative) must understand the nature of the study and sign the informed consent.

Exclusion Criteria:

• History of substance dependence within the past 2 months
• Major medical problems precluding the use of clozapine
• Pregnancy or lactation
• A serious suicide/homicide risk