Ciprofloxacin, a 4-quinolone bactericidal antimicrobial, has a high activity against a broad spectrum of bacterial microorganisms, including Pseudomonas aeruginosa. The fact that ciprofloxacin can be administered orally would represent a cost-efficient advance in the management of patients with cystic fibrosis, most of whom must be treated frequently with anti-pseudomonal antibiotics. In this study, 11 adult patients received 26 therapeutic courses of ciprofloxacin at a dose of 750 mg orally every 12 hours. In addition, a 13-year-old patient received 500 mg orally every 12 hours. The length of therapy was usually two weeks, but some patients received treatment for up to eight weeks. The mean serum concentration at two to three hours after administration of a dose was 3.68 micrograms/ml (range, 1.85 to 7.25 micrograms/ml). The mean trough level was 0.85 microgram/ml (range, 0.36 to 1.65 micrograms/ml). A comparable group of 11 patients matched by age and severity of disease were treated with conventional doses of tobramycin and azlocillin administered intravenously for at least two weeks. Sputum cultures from all the patients grew P. aeruginosa, except for one patient with Pseudomonas cepacia infection; the minimal inhibitory concentration of ciprofloxacin for these organisms ranged from 0.05 to 1.56 micrograms/ml. The clinical and microbiologic results obtained with these two antimicrobial regimens were similar. A therapeutic failure was noted in the patient infected with P. cepacia whose organism became resistant after one week of therapy (minimal inhibitory concentration greater than 4.58 micrograms/ml). Emergence of resistant strains was not observed in any of the other patients.