Comorbidity of psychosis and substance abuse has gained increased attention for some time. However, pharmacological treatment for opioid dependence among psychotic patients is seldom described. We present the treatment of four opioid dependent psychotic patients with methadone and antipsychotic medication. Three of the four patients had initially a period of increased psychotic symptoms, but all four patients have shown marked improvement following the introduction of methadone. Compliance with treatment has increased, they have had enduring non-psychotic periods and a markedly reduced use of illegal substances. The results should obviously be interpreted with caution, given the small number of subjects. Further research is therefore important.