Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures. Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection. Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood. Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic. In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature. Both elimination half-life (67 +/- 19 minutes versus 93 +/- 23 minutes) and the volume of distribution (16.8 +/- 5.3 liters versus 25.2 +/- 11.9 liters) increased when compared with the preoperative state. The increased volume may be due, in part, to redistribution of fluid. Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function. Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients.