Serum fentanyl concentrations were measured before, during, and after cardiopulmonary bypass and correlated with changes in total protein, albumin, hematocrit, pH, and PCO2 in five patients undergoing cardiac surgery. Serum fentanyl concentrations, total protein, albumin, and hematocrit declined with initiation of bypass but remained unchanged thereafter. PCO2 and pH did not change. In an additional seven patients, simultaneous pulmonary-artery and radial-artery fentanyl concentrations were measured. During bypass, when little, if any blood flowed through the pulmonary circulation, pulmonary artery fentanyl concentrations were higher than systemic arterial concentrations, but when lung ventilation and perfusion were restored, radial artery concentrations rose and pulmonary artery concentrations fell, indicating fentanyl sequestration in the lungs during bypass.