In the context of a previous WHO collaborative study, six research centers reported that naloxone (0.3 mg/kg) produced significant improvement in symptomatology in neuroleptic-treated patients. In the current Phase II WHO study, repeated (4 days) naloxone (0.3 mg/kg) administration was performed in schizophrenic patients (n = 43) from five WHO collaborating centers using a double-blind, placebo-controlled design. Both naloxone and placebo administrations were associated with significant reductions in symptoms. Naloxone, however, was not superior to placebo. These data are discussed in relation to endorphin hypotheses of schizophrenia.