The epidural administration of morphine and fentanyl delay the regression of sensory anesthesia in postoperative patients receiving epidural bupivacaine. This study was performed to determine any differential effects of two lipid-soluble opioids upon regression of sensory anesthesia during coadministration with epidural bupivacaine. Forty-eight patients scheduled for total knee replacement underwent lumbar epidural catheterization and received 1.5% etidocaine with 1:200,000 epinephrine to establish sensory anesthesia to approximately T6 bilaterally. Patients were randomized by the investigational pharmacy to receive either: (a) bupivacine without opioid (control) (n = 16), or (b) bupivacaine with 1 mg/mL of meperidine (n = 16), or (c) bupivacaine with 3 μg/mL of fentanyl (n = 16) in a double-blind fashion. Intraoperatively, 0.5% bupivacaine ± opioid was administered by epidural infusion at a rate of 10 mL/h. Postoperatively, the bupivacaine concentration was decreased to 0.25% (± the same opioid), and the infusion rate was decreased to 4 mL/h. Pinprick sensory anesthesia and verbal numerical pain score were recorded each hour after surgery by a blinded investigator. For each patient, the study was considered terminated when the cephalad level of sensory anesthesia bilaterally decreased five dermatomal segments or the pain score reached “5” (moderate pain). Patients receiving epidural infusions of bupivacaine and meperidine had a significantly slower regression of sensory anesthesia and slower development of pain. There was no difference in the rate of regression of sensory anesthesia or the development of pain among patients receiving bupivacaine alone or bupivacaine with fentanyl.