Ciprofloxacin (750 mg orally twice a day) was used to treat 22 episodes of methicillin-resistant Staphylococcus aureus (MRSA) colonization among 20 patients. Most patients had serious, progressive underlying medical diseases and had multiple sites of colonization. Eleven had previously received parenteral vancomycin therapy. Duration of ciprofloxacin therapy was from seven to 28 days. Therapy was discontinued in eight patients because of minor adverse reactions (two patients) or serious events attributed to underlying diseases (six patients). These serious events included seizures in two patients with known seizure disorders. Of the remaining 14 courses of therapy, 11 (79 percent) were associated with eradication of MRSA colonization. For the 18 patients who received at least two weeks of therapy, results of cultures from 47 of the 56 colonized sites became negative. Recolonization with MRSA occurred in four patients within one month. Increased resistance to ciprofloxacin was observed in seven of the 22 treatment episodes; this was associated with treatment failure in three patients and successful therapy in one patient; therapy was discontinued for other reasons in three patients. For comparison, medical records of 31 patients whose clinical specimens revealed MRSA but who did not receive ciprofloxacin were reviewed. MRSA colonization (as opposed to infection) was not eradicated in any patient who received only a single drug or no specific therapy directed against MRSA; four of seven patients given combination therapy had colonization eradicated. Although there is the potential for increased resistance, ciprofloxacin is an important new option that can be used as a single agent for eradication of MRSA colonization. Additional study is needed to define the optimum use of ciprofloxacin as a single agent and in combination therapy for MRSA colonization and infection.