A small but significant percentage of opioid-dependent patients will require neuroleptic treatment. Several classes of drugs have been shown to affect opioid metabolism. Two patients who were hospitalized with a diagnosis of opioid dependence received concomitant treatment with opioids and risperidone. After receiving risperidone for several days, both patients exhibited symptoms of opioid withdrawal despite having no change in their opioid doses. These withdrawal symptoms resolved soon after risperidone was discontinued. This finding suggests the possibility that risperidone may precipitate opioid withdrawal in opioid-dependent patients.