During cardiopulmonary bypass (CPB), several factors affect drug disposition and action. This topic has not been studied extensively during normothermic CPB. In this study, we related propofol dose to plasma propofol concentration and burst suppression of the EEG during normothermic bypass.After institutional approval and informed consent, 45 patients having cardiac surgery were assigned randomly to receive propofol infusions at 4 (Group A), 5 (Group B) and 6 (Group C) mg kg(-1) h(-1) during normothermic CPB. In all patients, small to moderate doses of fentanyl were also administered. Plasma propofol concentration and burst suppression ratio (BSR) were measured at the following times: (1) 10 min before CPB, (2) 10 min after the start of CPB, (3) 30 min after the start of the CPB, (4) just after aortic declamping, and (5) 60 min after CPB.At baseline, plasma propofol concentrations were similar among the three groups. After the start of CPB, the concentrations of propofol decreased significantly by 41, 35, and 30% of control values in Groups A, B, and C, respectively. In Group A, the concentration of propofol during CPB remained unchanged at less than the concentration before bypass. In Groups B and C, plasma propofol concentrations gradually increased during CPB to the pre-bypass concentrations. In Group A, BSR values did not change significantly during CPB. In Groups B and C, BSR values gradually increased and became significantly greater than baseline values. No patient reported intraoperative awareness.The pharmacokinetics and pharmacodynamics of propofol change during normothermic CPB. During normothermic CPB, the efficacy of propofol may be enhanced compared with before CPB.