Serum samples from 37 patients with cystic fibrosis (CF), whose lungs were colonized by Pseudomonas aeruginosa, were tested in a 1 yr prospective study to examine a possible relationship between levels of circulating immune complexes (CIC) and the following parameters: level of specific antibodies to P. aeruginosa; relative importance of P. aeruginosa mucoid and non-mucoid strains isolated from sputum; the forced expiratory volume (FEV1; percentage predicted); the chest X-Ray score (Brasfield system) and the clinical score (Shwachman system). Reactivity of CIC against P. aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Escherichia coli antigens were also assayed. We found that the FEV1, the chest X-Ray and the clinical scores were significantly lower in patients with high levels of CIC than in those with normal levels of CIC (p less than 0.001 for each). We also found that the level of IgG antibodies against P. aeruginosa was significantly higher (p less than 0.001) in patients with high levels of CIC than in those with normal levels of CIC. 78% of patients with high levels of CIC had predominantly mucoid P. aeruginosa isolates whereas only 21% of patients with normal levels of CIC had also predominantly mucoid P. aeruginosa isolates. Specific antibodies to P. aeruginosa were detected in all CIC isolated by polyethylene glycol precipitations from CF patients exhibiting both high levels of CIC and inferior pulmonary status. Our findings support the hypothesis that a high level of CIC in association with an aggressive humoral response to P. aeruginosa correlates with defective pulmonary status in cystic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)