Background.Decreased morphine requirements have been reported after liver transplantation when compared with other types of major abdominal surgery. The aim of this study was to examine plasma concentrations of three neuropeptides involved in pain modulation-metenkephalin (ME), beta-endorphin (BE), and substance P (SP)-in patients undergoing orthotopic liver transplantation (OLT) and in control patients undergoing other liver operations. We then compared the postoperative analgesic requirements in these two groups of patients.Methods.Plasma levels of ME, BE, and SP were measured by radioimmunoassay at preincision, preemergence, and for 3 days after operation in 13 patients undergoing OLT and in 10 control patients. Patient-controlled analgesia morphine delivery was recorded for all patients postoperatively, and plasma morphine, its metabolites, and patient pain and sedation scores were also measured.Results.ME levels were elevated in all OLT patient samples when compared with control patient samples. BE levels were not significantly different at any time. SP levels were significantly decreased only in preincision and preemergence OLT patient samples. Total patient-controlled analgesia morphine delivered during the first 3 postoperative days was significantly less in OLT patients (70±8 mg) than in control patients (101±12 mg). Plasma morphine, morphine-3-glucuronide, and morphine-6-glucuronide levels were decreased in OLT patients, however, statistical significance was seen only in the morphine-6-glucuronide results.Conclusions.We have shown that postoperative analgesic requirements are decreased in OLT patients, and we suggest that associated increased peripheral ME levels may be contributing to this decreased requirement. Based on our results, circulating BE and SP are less significant factors affecting postoperative analgesic requirements.