The pharmacokinetics of prophylactic antibodies may differ in cardiac and aortic aneurysm surgery for at least two reasons: aortic aneurysm surgery generally entails a greater blood volume loss and replacement, and aortic aneurysm surgery usually does not require extracorporeal cardiopulmonary bypass. We prospectively studied two different cefamandole dosing regimens in patients undergoing aortic aneurysm surgery (phase 1, 1 gm intravenously at the induction of anesthesia; phase 2, 2 gm intravenously at the induction of anesthesia followed by 1 gm intravenously every 2 hours during surgery). In phase 1 and 2 plasma levels were measured at the time of skin incision, aortic cross-clamping, aortic unclamping, and skin closure. In phase 2 cefamandole elimination in urine and cell-saver effluent was also determined. An adequate plasma level of 10 micrograms/ml was maintained in only 4 of 14 patients in phase 1, but in 10 of 10 patients in phase 2. Cefamandole loss in cell-saver effluent was 136 +/- 100 mg, which was 13% of the measured renally excreted amount. As has been previously shown in cardiac surgery, a cefamandole prophylactic antibiotic regimen of 2 gm intravenously at the induction of anesthesia followed by 1 gm every 2 hours during surgery provides a dependable and practical dosing regimen in patients undergoing aortic aneurysm surgery.