The relationships between plasma or brain concentrations and analgesic effects of both buprenorphine (BN) and an active metabolite, norbuprenorphine (NBN), were investigated in rats. Maximal analgesic effects measured by a tail flick test were obtained at 10 and 30 min after intravenous (i.v.) administration of BN (8 micrograms/kg dose) and NBN (100 micrograms/kg dose), respectively. No correlation was observed between analgesic effect and the early plasma BN or NBN concentrations. However, at latency times, the concentration of BN in the plasma, cerebellum and the rest of the brain (including the brainstem, midbrain and cerebrum) was related in a counterclockwise hysteresis fashion to analgesia. There was no relationship between the estimated specific binding concentration of BN in the brain and the analgesic effects. After i.v. administration of BN or NBN, the analgesic effect of NBN was approximately one-fiftieth that of BN. The n-octanol/water partition coefficient of NBN was one-tenth that of BN. Further, the results of intraventricular administration of each drug suggested that the intrinsic analgesic activity of NBN was one-fourth that of BN. From these findings, we conclude that the remarkably weak pharmacological effect of NBN after i.v. administration may be due not only to the low permeability of NBN into the brain but also to its small intrinsic pharmacological effect.