The effects of short- and long-term neuroleptic therapy on peripheral secretion of β-endorphin (β-EP) and β-lipotropin (β-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10–18 mg/day). The other 9 patients were given a combination of haloperidol (6–30 mg/day) with either chlorpromazine (25–75 mg/day), clotiapine (40–60 mg/day), or fluphenazine decanoate (25–75 mg/month) for 14–18 months (group C). β-EP and β-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. β-EP mean basal levels were higher in patients than in controls; however, β-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while β-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of th