To evaluate the biosynthetic activity of the pineal gland in schizophrenia, the circadian rhythm of plasma melatonin was investigated in 9 drug-free chronic schizophrenics and in matched healthy subjects. In 7 of the patients, the 24-hour secretory pattern of the pineal hormone was reassessed after 10 weeks of treatment with antipsychotic drugs. In drug-free schizophrenics, the nocturnal increase in plasma melatonin levels was significantly blunted as compared to healthy subjects (p < 0.0001). Chronic treatment with antipsychotic drugs significantly improved psychotic symptomatology, but did not change the secretory pattern of melatonin. These data show that the biosynthetic activity of the pineal gland is impaired in chronic schizophrenia and that successful treatment with antipsychotic drugs does not go parallel with changes in the production of melatonin.