The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte: plasma partition, and heptane: water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.