BACKGROUND This study was designed to compare the efficacy of epidural vs. intravenous administration of alfentanil for treatment of postoperative pain. METHODS Twenty patients were randomly allocated to one of the two study groups to receive either an epidural bolus dose (0.75 mg) followed by an epidural infusion (0.36 mg/h) (EPI group) or an intravenous infusion (0.36 mg/h) of alfentanil (IV group) for 24 h. These dose regimens were chosen such that equivalent and subanalgesic plasma concentrations of alfentanil were obtained. PCA-morphine was available to both groups. Morphine consumption, pain scores measured on a Visual Analogue Scale (VAS) and the number of demands were used as variables to evaluate the efficacy of the postoperative analgesic therapy. In addition, plasma concentrations of alfentanil were measured. RESULTS The mean plasma concentrations of alfentanil were similar and < 20 ng/ml in both groups. Total morphine consumption (EPI: 40 mg, i.v.: 43 mg), pain scores (time when the VAS-score > 3.0: EPI: median 215 min; i.v.: median 215 min) and number of valid demands (EPI: median 25; i.v.: median 34) did not differ between the groups. CONCLUSIONS Compared to intravenous infusion of alfentanil epidural infusion resulting in the same plasma concentrations is not more effective in relieving postoperative pain. In view of this observation we were not able to demonstrate a spinal mechanism of alfentanil.