Recent reports indicate that methicillin-resistant Staphylococcus aureus (MRSA) may be emerging as a significant pediatric nosocomial pathogen. Children with cystic fibrosis (CF) pulmonary disease are subject to many of the risk factors for MRSA colonization and/or infection. We retrospectively investigated the prevalence and significance of MRSA from sputum and throat cultures in 452 patients with CF followed during 1986. No MRSA had been isolated during 1984 or 1985. Although S. aureus was isolated from 212 patients (47%) in 1986, only 14 (3%) showed MRSA. The MRSA strains had 11 different antimicrobial susceptibility patterns. Neither age, clinical condition, nor recent prior hospitalization correlated with MRSA acquisition. Acquisition did not appear to directly affect the course of the pulmonary disease in these patients even though no patient received any treatment for their MRSA. The prevalence of MRSA is low, although patients with CF are subject to many risk factors. MRSA appears to be mainly community-acquired and to represent colonization rather than infection. However, the potential for nosocomial MRSA infection is present, and vigilance is required in monitoring any changes in frequency of isolation or infection with these organisms.