Using a rabbit sterile peritonitis model, we compared the penetration of intravenously administered amikacin, gentamicin, and penicillin G into peritoneal exudate. Peritonitis was induced with sterile normal saline, and the peritoneal exudate contained 23,751 +/- 3,039 granulocytes 8 h later. Antibiotics were administered intravenously 3 h after initiating peritonitis, and serum and peritoneal fluid concentrations were measured for 5 h. Peritoneal levels of each antibiotic exceeded simultaneous serum levels by 1 h after dose and remained above serum levels thereafter. The maximum peritoneal fluid concentration of amikacin reached 71.2% +/- 12.7 of the maximum serum concentration, whereas maximum gentamicin peritoneal concentration achieved 37.1% +/- 2.7, and penicillin achieved 23.2% +/- 4.5, of their respective maximum serum concentrations.