This study will examine the physical responses brought on by clozapine and haloperidol in people experiencing their first episode of schizophrenia.

This is a longitudinal double blind, 2- 5 year study of the clinical, neuroendocrine and biochemical response to clozapine (CLOZ) and haloperidol (HAL) in a group of "first episode" schizophrenic (RDC) patients. Within the protocol, we compare the differential effects of the two drugs over the short term (12 weeks) and the long-term (2-5 years); we evaluate the relationship between change in prolactin level and clinical response of the patients; and we search for biochemical predictors and correlates of clinical response. To achieve the study aims, we employ a drug-washout period, a 12-week acute treatment period; and an 88 - 260 week follow-up period.

Inclusion Criteria:

• RDC diagnosis of schizophrenia
• Men and women, without regard to race/ethnicity,
• Aged 18-45
• Acutely psychotic with a score of at least 3 on one of the psychotic scale items of the Brief Psychiatric Rating Scale (BPRS) (hallucinations, delusions, conceptual disorganization) and a total BPRS of > 21 (on a 0 - 6 scale);
• Require treatment with neuroleptic drugs on a clinical basis;
• The patient (or the patient's authorized legal representative) must understand the nature of the study and sign the informed consent;
• Be within the first episode of a psychotic disorder;
• Have a history of neuroleptic treatment of < 12 weeks;
• Likely to remain in the study for 2 years.

Exclusion Criteria:

• Substance dependence in the last six months
• History of seizure or blood dyscrasia
• Major medical illness
• Pregnancy or Lactation