Propranolol may be uniquely useful in cardiac surgical procedures, since beta adrenergic blockade can prevent the hypokalemia and associated arrhythmias which result from systemic hypothermia. To determine the effects of hypothermic cardiopulmonary bypass (HCPB) on the in vivo handling of propranolol, serial drug plasma concentrations (Cp) were measured during HCPB in 12 patients who had been treated chronically with propranolol prior to surgery. Although no further propranolol was given during the procedure, Cp values (corrected for plasma volume dilution) were higher during hypothermia than in the preoperative period, falling to or below control levels after rewarming. Due to the variables inherent in patient surgery, meaningful kinetic analysis could not be carried out. Therefore, intravenous propranolol (1 mg/kg) was given twice to each of 5 dogs, first after anesthesia only, then after anesthesia and systemic cooling to 26 degrees in a water bath Cp values measured serially over 2 hr after drug administration were consistently higher during hypothermia. Compared with the paired normothermic control studies, hypothermia markedly reduced the apparent volume of distribution (6.78 +/- 1.65 vs 2.08 +/- 0.58 L/kg; p less than 0.001) and the total body clearance of propranolol (64.4 +/- 11.0 vs 32.3 +/- 7.2 ml/kg/min; p less than 0.005). These data show that hypothermia substantially alters the pharmacokinetics of propranolol, resulting in plasma drug levels higher than those predicted from kinetic patterns derived under normothermic conditions.