This study compared enoxacin administered orally with cefoperazone administered intramuscularly for the treatment of Enterobacter aerogenes endocarditis in rabbits. The MICs and MBCs of both enoxacin and cefoperazone for an inoculum of 10(5) CFU/ml of the E. aerogenes strain used were 0.8 micrograms/ml, respectively. With an inoculum of 10(8) organisms per ml, enoxacin at 2 and 5 micrograms/ml and cefoperazone at 60 and 155 micrograms/ml were effective in reducing titers of E. aerogenes in broth. E. aerogenes endocarditis in rabbits was treated with enoxacin (100 or 25 mg/kg orally every 6 h) or cefoperazone (60 mg/kg intramuscularly every 6 h) for 5 or 10 days. Enoxacin at 100 and 25 mg/kg significantly reduced bacterial titers of vegetations compared with those of untreated controls. Enoxacin at 100 mg/kg was significantly more effective than enoxacin at 25 mg/kg and cefoperazone. Enoxacin at 25 mg/kg and cefoperazone did not differ significantly. Cefoperazone and controls did not differ significantly. In uninfected rabbits single doses of cefoperazone achieved much higher concentrations in serum than single doses of enoxacin (25 and 100 mg/kg). The half-lives of enoxacin at 25 and 100 mg/kg were approximately three times longer than that of cefoperazone.