Although interactions between opioids and adrenergic agonists in the treatment of pain have been demonstrated in humans, the contribution of specific adrenergic receptors in this interaction remains to be clarified. In a double-blind, placebo-controlled study in male patients with postoperative dental pain, we investigated the effect of preoperative administration of the alpha 2-adrenergic antagonist, yohimbine, on analgesia produced by postoperative intravenous morphine. Although yohimbine by itself did not affect the pain, the overall analgesic effect of morphine was significantly enhanced in the presence of yohimbine. This report is the first to demonstrate that an alpha 2-adrenergic antagonist enhances opiate analgesia in humans.