Rhinoscleroma, a chronic progressive infection of the nose and associated structures caused by Klebsiella rhinoscleromatis, has posed a therapeutic dilemma since its identification in the late 1800s. Although a number of antibiotics have been found to be effective in this relapsing disorder, the lengthy duration of treatment can lead to problems with adverse effects and compliance, especially with the traditional therapies of streptomycin and tetracycline. We report on a patient with extensive nasal rhinoscleroma who achieved pathologic and bacteriologic resolution during treatment with oral ciprofloxacin after previous courses of tetracycline and trimethoprim-sulfamethoxazole. Ciprofloxacin may prove to be useful in the therapy of rhinoscleroma because it is convenient for oral administration, achieves good tissue levels, is concentrated in macrophages, and is generally well tolerated as long-term therapy. As mentioned in a recent review of patients with rhinoscleroma at the Mayo Clinic, the fluoroquinolones deserve further study as potentially highly effective agents for this uncommon but significant infectious condition.