Flavobacterium meningosepticum is an uncommon cause of adult nosocomial infection. On a medical/surgical intensive care unit we recently encountered an adult outbreak of respiratory colonization and infection caused by this organism, which was associated with the prophylactic use of aerosolized polymyxin B that had been used in an attempt to abort an outbreak of infection caused by highly resistant strains of Pseudomonas aeruginosa. Twenty isolates (95% from respiratory secretions) of F. meningosepticum from nine persons were identified during a 2 1/2-month period. No environmental source has been identified to date. Pneumonia developed in five patients, and two deaths associated with this organism occurred. All isolates were sensitive to ciprofloxacin; none were sensitive to other antibiotics tested, including third-generation cephalosporins, aminoglycosides, erythromycin, trimethoprim-sulfamethoxazole, antipseudomonal penicillins, aztreonam, and imipenem/cilastatin. Two patients with nosocomial pneumonia were successfully treated with oral ciprofloxacin. F. meningosepticum may emerge as an important pathogen if prophylactic use of polymyxin B becomes more widespread. Ciprofloxacin may become the agent of choice for treatment of this organism.