Animal models of infection are very useful tools for identifying those situations in which antibacterial drugs, including the quinolones, may play special roles, i.e., for positioning a drug correctly for its role in the treatment of human disease. Ciprofloxacin has been studied extensively in discriminative animal models of infection, and its efficacy in the treatment of these infections has been compared with that of standard therapy. In a rabbit model of staphylococcal endocarditis, ciprofloxacin was as effective as nafcillin alone, as well as nafcillin and gentamicin in combination, in treating rabbits with methicillin-susceptible Staphylococcus aureus endocarditis. Additionally, its activity was equal to that of vancomycin in reducing vegetation titers in rabbits with methicillin-resistant staphylococcal endocarditis. In a rabbit model of pseudomonal meningitis, ciprofloxacin was as effective as the combination of ceftazidime and tobramycin in lowering bacterial titers. However, in this model, serum levels of ciprofloxacin (6 micrograms/ml) necessary to achieve a bactericidal effect in the cerebrospinal fluid were slightly higher than levels targeted for humans. In a model of pseudomonal pneumonia in neutropenic guinea pigs, the efficacy of ciprofloxacin was compared with that of tobramycin and ceftazidime, both alone and in combination: ciprofloxacin was as effective in lowering bacterial counts as was the combination of ceftazidime plus tobramycin and its activity was superior to that of either drug alone. Thus, data from studies of ciprofloxacin in the treatment of endocarditis, meningitis, and pneumonia in animal models of infection suggest that this quinolone may play an important role in the therapy of these difficult-to-manage infections in humans.