To evaluate the prognostic significance of the age at onset of chronic Pseudomonas aeruginosa colonization (OPCP) with respect to pulmonary disease progression in patients with cystic fibrosis (CF), a retrospective long-term analysis using annual chest radiographs was performed on 54 CF patients. Thirty-seven patients (68%) were chronically colonized before the age of 12 years (group 1), 17 patients (32%) thereafter (group 2). These two groups did not significantly differ in terms of mean duration of follow up (16.2 +/- 5.9 years), sex, CF genotypes, colonization with other respiratory pathogens, supportive medical treatment and death rate during the study period. Chest radiographs were evaluated according to the Chrispin-Norman score, increasing scores representing increasing severity of respiratory disease. In both groups, progression of score means was not accelerated of score means was not accelerated up to 6 years after OCPC (Scores at OCPC set 0; mean score +/- SEM 6 years prior to OCPC -5.6 +/- 2.0; 10 years after OCPC +3.6 +/- 0.7 points). Patients chronically colonized prior to age 12 years (group 1) scored significantly higher between age 2 and 11 years (maximum difference at age 8 years [mean +/- SEM]: 9.4 +/- 0.7 vs. 4.3 +/- 1.3 points; P = 0.002) as compared to group 2. After age 11 years, mean scores were similar in both groups, since in group 2 scores increased rapidly after age 8 years. We conclude that OCPC did not cause an immediate acceleration of CF lung disease judged by serial chest radiographs. Rapid progression in group 2 (OCPC after age 12 years) was independent of OCPC since it occurred earlier. These data indicate that OCPC may be a marker rather than the cause of respiratory disease progression.