The efficacy of cefepime, a new broad-spectrum cephalosporin, was compared with those of cefpirome, ceftazidime, vancomycin, imipenem-cilastatin and penicillin G in a rat model of endocarditis caused by a methicillin-susceptible strain of Staphylococcus aureus. Rats were infected intravenously with approximately 10(5) cfu of a penicillin-resistant strain of S. aureus 24 h after placement of a catheter into the left ventricle of the heart via the carotid artery. Efficacy was evaluated by comparing bacterial counts in the cardiac vegetations of treated rats with those of untreated controls. Rats treated with cefepime, cefpirome, ceftazidime, imipenem-cilastatin and vancomycin showed a reduction in the number of bacteria recovered from cardiac vegetations compared with infected control animals; penicillin G was ineffective in this respect. Serum concentrations of the study antimicrobials were determined at selected times following the administration of a single subcutaneous dose. The pharmacokinetic parameters of the cephalosporins were similar in these animals. This study shows that cefepime may be of value in the treatment of staphylococcal endocarditis.