The incidence and prevalence of Pseudomonas cepacia pulmonary colonization were noted to be increasing in patients with cystic fibrosis (CF). Previous work had indicated a greater prevalence of P. cepacia among siblings (with CF) of patients colonized by P. cepacia as well as an association of initial positive P. cepacia cultures with a hospitalization. Because of uncertainty regarding the source and mode of transmission, limited precautionary measures were instituted in 1983, including physical separation of hospitalized patients colonized with P. cepacia from non-colonized patients, reeducation of staff concerning basic infection control procedures, explanation to families regarding these precautionary efforts, and institution of separate summer camp sessions. Repeated environmental cultures throughout the hospital were negative for P. cepacia. Coincident with the institution of control measures, a sharp decline in incidence occurred (8.2% in 1983 versus 1.7% in 1984). These results are suggestive of patient-to-patient transmission. Because P. cepacia infections have been associated with shorter survival in some patients with CF, we will continue our current segregation measures.