Antibiotic prophylaxis in cardiac surgery is recommended to combat acquired infections caused by staphylococci and gram-negative bacilli. Prophylaxis seems effective provided blood levels are greater than minimal inhibitory concentrations (MIC). In this study, two doses of antibiotics were compared in 45 patients with normal renal function during cardiopulmonary bypass (CPB). All patients received 50 mg/kg of oxacillin. Group 1 (30 patients) also received 1 mg/kg of tobramycin, while group 2 (15 patients) received 2 mg/kg of tobramycin. Blood samples were taken after the administration of antibiotics, as well as at the onset and conclusion of CPB. Additional samples were taken before and after heparin injection before CPB, and from the arterial and venous cannulae of the bubble oxygenator during CPB. In both groups, oxacillin serum levels were constantly greater than MIC for susceptible bacteria. In group 1, tobramycin levels less than 2 micrograms/mL (MIC for most susceptible bacteria) occurred in four patients before CPB, in 14 patients at the onset of CPB, and in 19 patients at the conclusion of CPB. These low levels were not explained by heparin administration or absorption onto the CPB circuit, but were the result of hemodilution. In group 2, in which all the tobramycin levels were higher than 2 micrograms/mL, serum levels decreased from 9.9 +/- 3.4 (mean +/- SD) to 3.7 +/- 0.7 micrograms/mL throughout the procedure. Plasma creatinine did not change significantly in either group. It is concluded that in patients with normal renal function, doses as high as 50 mg/kg of oxacillin and 2 mg/kg of tobramycin may be necessary before CPB to provide adequate serum levels throughout CPB.