Opioids can have mood-elevating effects in healthy subjects and have been used successfully to treat refractory depressed patients. A few case reports indicate that opioid analgesics can induce mania. The authors investigated the mood reaction of opioid analgesics in patients with bipolar disorder. Nine (27%) of 33 patients who took opioid analgesics for medical reasons experienced a significant hypomanic/manic reaction, and two other patients reported an antidepressant effect. None of the comparison subjects reported a significant mood reaction from opioid analgesics. These results indicate that opioid analgesics can have an important mood-altering effect on patients with known bipolar disorder.