The objective of this study was to identify risk factors of significance for acquisition of Pseudomonas aeruginosa by children with cystic fibrosis (CF). Our working hypothesis is that exposure of infants and young children with CF to older, infected patients increases their risk for acquiring this organism. A special opportunity arose to study this question in detail, as we have been performing a randomized clinical trial of neonatal screening for CF throughout the state of Wisconsin during the period of 1985-1994. Patients were selected for this study based on either early identification through screening or diagnosis by standard methods. A longitudinal protocol employed at Wisconsin's two CF Centers includes routine cultures of respiratory secretions and collection of clinical, demographic, and activity information on patients and their families. Previous observations in our trial revealed that one center at an old hospital in an urban location showed a significantly shorter time to acquisition of P. aeruginosa for CF patients followed there. To study the center effect further, we performed statistical analyses using survival curves and stepwise regression analysis of all life history covariates available. The results of these analyses showed that the statistically significant correlations involve the following risk factors: 1) center and old hospital (r=0.42); 2) center and original physician (r=0.61); 3) center and exposure to pseudomonas-positive patients (r=0.29); and 4) population density and urban location (r=0.49). The final statistical model demonstrated that increased risk due to aerosol use (odds ratio=3.45, P=0.014) and a protective effect associated with education of the mother (odds ratio=0.81, P=0.024) were the most significant factors for acquisition of P. aeruginosa. The previously observed center effect was confined to the 1985-1990 interval at the old hospital (odds ratio=4.43, P < 0.001). We conclude that multiple factors are involved in increasing the risk of young children with CF to acquire P. aeruginosa, and that the observed center effect can best be explained by a combination of factors. These results suggest that facilities and methods used to care for young children with CF can significantly influence their likelihood of acquiring pseudomonas in the respiratory tract.