The opiate antagonist, naloxone, produces dose-dependent biphasic changes in clinical pain. The mechanism of the analgesia produced by low dose naloxone is unknown. To study the analgesic effect of naloxone, we have used a programmable infusion pump, which eliminates placebo-induced endorphin-mediated analgesia, to administer different doses of naloxone. We report that use of machine infusion of naloxone exclusively produces analgesia. The implications of this finding to the mechanism of naloxone-induced analgesia are discussed.