The objectives of the study were: (1) comparison of hypoalgesic effects of pre- and post-traumatic epidural morphine (EM) on primary and secondary hyperalgesia, and (2) comparison of EM hypoalgesia in normal and injured skin. Burn injuries (25 x 50 mm rectangular thermode, 47 degrees C, 7 min) were produced on the calves of healthy volunteers, at 2 different days at least 1 week apart. In randomized order, the subjects received 4 mg of EM administered via the L2-L3 intervertebral space on one day and no treatment on the other day. One calf was injured 30 min prior to and the other calf 2.5 h after administration of morphine. Hence, the calf injured prior to morphine administration was a model of postinjury treatment, and the calf injured after morphine administration, a model of pretraumatic treatment. The timing of injuries was identical on the morphine treatment and control days. The injuries induced decrease in heat pain detection and tolerance thresholds within the area of injury (area of primary hyperalgesia) as well as reduction of areas of allodynia for brush and pinprick surrounding the injury (area of secondary hyperalgesia). Both pre- and post-traumatic administration of EM increased heat pain detection and tolerance thresholds, and decreased by approximately 50% the areas of secondary hyperalgesia 2.5 h postinjury. The effects of morphine were naloxone (NAL)-reversible (0.1 mg/kg, i.v.). There was no significant difference between pre- and post-traumatic administration of morphine on the effect of either primary or secondary hyperalgesia. EM increased the heat pain detection threshold more within the injury than at a corresponding non-injured site. There was no significant difference in the effect of morphine on heat pain tolerance in injured and non-injured skin. Following NAL, the areas of secondary hyperalgesia expanded beyond control size. It is suggested that the major effect of EM on secondary hyperalgesia is inhibition of C fibre-mediated activity which maintains the altered response properties of central neurons responsible for secondary hyperalgesia. Possible mechanisms of action of NAL in enhancement of hyperalgesia are discussed.