A randomized double-blind study compared the dose-response relationship of epidural morphine for postoperative pain relief in two groups of patients whose surgical procedures would result in either moderate (femoral-popliteal bypass) or severe (total knee replacement) postoperative pain. Preservative- free morphine sulphate in doses of 0, 2, 5, or 10 mg in a volume of 10 ml saline were administered via lumbar epidural catheters. The epidural morphine was administered 1 hr after the last dose of intraoperative local epidural anesthetic in an effort to achieve a pain-free postoperative course. A significant relationship existed between the dose of epi- dural morphine and both time to first required pain medication and 24-hr weighted pain score. Five mg epidural morphine provided significant improvement in postoperative analgesia compared with the control in both groups. Further enhancement of analgesia occurred with 10 mg; however, late respiratory depression, demonstrated by an increased resting PaCO2 10 hr after administration, was seen only with the 10-mg dose in both surgical groups. Minor complications such as nausea, vomiting, pruritus, and urinary retention were uncommon and did not appear to be related to dose. We found that 5 mg epidural morphine provided long-lasting postoperative analgesia without serious adverse effects after peripheral vascular and orthopedic surgery.