We have studied plasma protein binding of alfentanil in 10 patients given a mean total dose of 949 micrograms kg-1 as the principal anaesthetic agent for coronary artery bypass grafting. The mean unbound fraction of plasma alfentanil increased from 0.09 to 0.16 after administration of heparin and to 0.26 after beginning cardiopulmonary bypass (CPB). After CPB until the end of surgery, the unbound fraction decreased to 0.12. These changes in the unbound fraction were associated with significant changes in plasma total and unbound concentrations of alfentanil also. Within the first 1 min of CPB, total alfentanil concentration had decreased by more than the unbound concentration and the decrease observed in the latter disappeared rapidly. From induction of anaesthesia until awakening of the patient, plasma protein binding of alfentanil was related significantly (P = 0.0166) to the serum concentration of orosomucoid (alpha 1-acid glyco-protein).