With the initiation of cardiopulmonary bypass (CPB), using a membrane oxygenator, the drop in circulating fentanyl concentration is greater than can be attributed to dilution alone. This study examined the Scimed brand (2A-800) membrane oxygenator as a site of fentanyl binding. Initial experiments used an assembled CPB circuit. Subsequent dissection and analysis of the oxygenator revealed that the silicone-based membrane sheets were the primary site of fentanyl binding. The silicone-containing waterproof wrapper was also responsible for 1 % to 2% of fentanyl binding. Binding of fentanyl to the Scimed membrane oxygenator occurs at a rapid rate and continues until the membrane has taken up 130 ng/cm2 of membrane surface area. The interaction is complete by 15 to 30 minutes if suprasaturated concentrations are used. Samples of membrane material with a surface area of 1 cm2 were also studied. Isolated membrane squares in a nonmoving prime solution required two hours for saturation at the same fentanyl concentrations as the intact membrane with circulating prime. Introduction of motion to the priming solution accelerated the rate of fentanyl binding by the isolated membrane squares to a rate similar to the intact membrane. Motion also provided results similar to those previously reported using different analysis techniques. Therefore, this method of studying fentanyl-membrane interactions using samples of membrane and tritiated fentanyl is a valid model for the intact membrane oxygenator in the assembled bypass circuit. In addition to solution movement, fentanyl concentration of the priming solution was also found to affect the rate of fentanyl uptake. When fentanyl concentrations were used which were insufficient to achieve saturation of the membrane (10 ng/mL and 20 ng/mL), the rate of uptake was slowed. Binding of all available fentanyl under these conditions occurred within three hours. There is potential modification of this interaction by several clinically relevant factors, including temperature, pH, protein content of prime solution, and other drugs. These areas require further study before the saturation data are applied to clinical practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27128/1/0000121.pd