The efficacy of ciprofloxacin alone and in combination with azlocillin was compared with that of azlocillin plus tobramycin in a rat model of aortic valve endocarditis due to Pseudomonas aeruginosa. MICs against the infecting strain of ciprofloxacin, azlocillin and tobramycin were 0.125, 8, and 0.5 mg/l, respectively. Antimicrobials were administered 24 h after bacterial challenge and for six days. Mean peak/trough serum levels for ciprofloxacin (50 mg/kg i.v. q 12 h), azlocillin (500 mg/kg i.v. q 12 h) and tobramycin (6.5 mg/kg i.v. q 12 h) were: 10.5/0.2, 386/less than 16, and 6.2/less than 0.6 mg/l, respectively. Ciprofloxacin alone was more effective than the combination azlocillin-tobramycin in increasing survival (p less than 0.05), sterilizing blood (p less than 0.05) and valves (p less than 0.001), and in reducing bacterial titers in vegetations (p less than 0.001). Ciprofloxacin-azlocillin combination was not more effective than ciprofloxacin alone. Drug resistance was not encountered in post-treatment isolates with any therapy regimen.