AbstractComplexation of various equipotent doses of fentanyl‐like opioids in hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) results in a potentiation of the spinal activity of these opioids after both epidural and intrathecal administration in a fixed diluent volume of 10 μl. The first active and mot optimal concentrations of HP‐β‐CD after epidural administration differed between the opioids and varied from 1 to 20% HP‐β‐CD. The duration of deep surgical analgesia increased at optimal concentrations of HP‐β‐CD with a factor 3 for fentanyl (15% HP‐β‐CD), 3.6 for sufentanil (5–10% HP‐β‐CD), respectively. Increasing the concentrations of HP‐β‐CD above these optimal concentrations did not further potentiate the analgesic activity of the opioids. The complexation of the opioids in HP‐β‐CD also increased the duration of supraspinal side‐effects. However, except for lofentanil, the potentiations of the analgesic activity were always longer lasting than those for the secondary side‐effects. As a consequence, there was a gain in the total time of analgesia without side‐effects. After intrathecal administration, there was no gain in the duration of deep surgical analgesia after complexation of fentanyl, carfentanil and alfentanil in HP‐β‐CD. For both sufentanil and lofentanil, maximal potentiation of analgesia was measured at 10% HP‐β‐CD with, respectively, 2.8‐ and 1.7‐fold increases in the duration of analgesia. Also intrathecally, there was some gain in the duration of duration of analgesia without supraspinal side‐effects. These results on the potentiation of the opoids with HP‐β‐CD are discussed in