To evaluate the relationship between Pseudomonas aeruginosa colonization and the development of lung disease, we studied 895 patients who attended our cystic fibrosis clinic between 1975 and 1988. The prevalence of P. aeruginosa colonization was 82%. Patients who acquired P. aeruginosa in the first year of life had a similar 10-year survival rate (85%) to that in patients who were colonized between the ages of 1 and 7 years (87%), and to that in patients colonized after the age of 7 years (78%). One year before colonization, mean age, forced expiratory volume in 1 second (FEV1), forced vital capacity, and forced expiratory flow in the mid-expiratory phase were similar to those in a group of patients who remained free of P. aeruginosa. No significant change in pulmonary function variables could be demonstrated 1 year and 2 years after the colonization. The rate and duration of hospitalization did not increase in the years after P. aeruginosa colonization compared with the years before colonization. By the age of 7 years, the mean percentage of predicted FEV1 was lower by 10% in patients who were already colonized by P. aeruginosa compared with those who were not colonized (p less than 0.01). A similar reduction in FEV1 was observed at all ages from 7 to 35 years, but no precipitate rate of decline in FEV1 could be associated with P. aeruginosa colonization. We conclude that although P. aeruginosa colonization is associated with 10% lower lung function, it does not cause an immediate and rapid reduction, as has been previously reported. The clinical course and the pulmonary deterioration in cystic fibrosis after P. aeruginosa colonization is a gradual and variable process.