In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.