OBJECTIVE: Gender differences in onset of illness, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. Patients with first- episode schizophrenia were examined to determine whether gender differences also occur in these patients. METHOD: Fifty-four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied beginning in an initial stage of the first hospitalization for psychosis while undergoing treatment with a standardized medication regimen. Before antipsychotic drug treatment and during 1 year of follow-up each patient was rated on the Schedule for Affective Disorders and Schizophrenia--Change Version (psychosis and disorganization items), Scale for the Assessment of Negative Symptoms, Clinical Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and prolactin levels were determined weekly for the first 6 weeks. RESULTS: The female schizophrenic patients had a later onset and better treatment response than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin levels from baseline to weeks 1 through 6 were greater among the women. CONCLUSIONS: Gender differences in onset and degree of treatment response in first-episode schizophrenic patients are similar to those of chronic patients and are apparent at early stages of the illness. The greater pharmacologic responsivity of the female patients, as indicated by the neuroendocrine results, is consistent with the gender difference in degree of symptom improvement with medication.