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Abstract Background and Purpose: In recent years, review of opioid system and its changes in the psychopathology of schizophrenia through thear probable role our on neuronal synopses and cell body of dopaminergic neurons and also decrease dopamine secretion from acumbans nuclei and effects of opium agonists in treatment of those patients has been adventajes for clinicians.Materials and methods: In a prospective double blind evaluation, 60 chronic schizophrenic inpatients on a stable regimen of neuroleptic medication with positive and negative symptom scale (PANSS) score of higher than 80 and were randomly assigned to either antipsychotic plus naltrexone or antipsychotic plus placebo. Thirty patients (30) received 100 mg/day of naltrexone plus antipsychotic drug while 30 received placebo plus antipsychotic drug for 6 weeks. PANSS scores were evaluated on the base of the study, biweekly through out the study and two weeks after the trial. The treatment effect was calculated by repeated measurement ANOVA.Results: Difference between four types of symptoms (positive symptom, negative symptom, general psychopathological symptom, total score of PANSS) in the case and control groups was not significant (P < 0.05). In supplement two (S2) scores, a statistically non significant difference was seen in two groups (P < 0.07). Conclusion: Additional treatment with 100 mg/day naltrexone in a 6 week trial had no significant therapeutic effect on typical or atypical antipsychotic drugs with regards to schizophrenia psychopathology. J Mazand Univ Med Sci 2008; 18(66): 10-18 (Persian)