A rabbit sterile peritonitis model was used to determine the relative penetration of four cephalosporin antibiotics into exudate fluid. Male New Zealand white rabbits were given 120 ml of sterile saline intraperitoneally, and peritonitis developed over the following 8 h, with exudate fluid containing a mean of 17,188 granulocytes per mm(3) at 8 h. Each antibiotic was administered intramuscularly at a dose of 30 mg/kg 3 h after peritonitis was initiated, and serum and peritoneal concentrations were measured 0.5, 1, 2, and 4 h later. Cefamandole gave the highest mean peak serum level (26.8 mug/ml), and cephalothin, cephacetrile, and cephradine all gave peak serum levels between 13 and 15 mug/ml. When peak peritoneal exudate concentration was expressed as a percentage of peak serum concentration, cephradine developed 28.5% of the peak serum level, cephacetrile 27.7%, cephalothin 14.0%, and cefamandole 12.5%. These percentages of exudate penetration were inversely proportional to the degree of serum protein binding: cephradine 26.6%, cephacetrile 36.3%, cephalothin 50%, and cefamandole 88%.