Recurrent respiratory infections associated with "mucoid" Pseudomonas aeruginosa characterize the advanced stages of cystic fibrosis. To determine if chronic antigenic stimulation is associated with circulating immune complexes (CIC), we assayed the sera of 20 hospitalized patients using the technique of precipitation with 4% polyethylene glycol. Elevated CIC levels, defined by > 310 micrograms IgG per ml, were found in 18 of 20 patients, (range, 350 to 3200 micrograms/ml). Serum, supernatant, and resuspended precipitates were assayed for hemagglutinating antibodies against pseudomonas lipopolysaccharide (LPS or endotoxin) and exotoxin A antigens. Both serum anti-LPS (range, 1:64 to 1:2048) and antitoxin titers (range, 1:64 to 1:16, 384) were markedly elevated and higher than titers in supernatants and resuspended precipitates, indicating antibody excess. "Enrichment" ratios for antibodies present in CIC were calculated by proportion of titer to immunoglobulin in the precipitated complex relative to these values in serum. Mean enrichment ratios of 13.1 and 13.9 were obtained for LPS antibody before and after 2 mercaptoethanol reduction, but the mean enrichment ratio for antitoxin was only 2.07. Serially diluted supernatants and precipitates were boiled for 1 hr and tested for endotoxin-like activity by the limulus test. At > 1:8 dilutions, precipitates were positive, and supernatants were negative. These findings indicate that CIC's are common in advanced cystic fibrosis, and analysis of the precipitated complexes demonstrates significant (> 13-fold) enrichment of antibodies against LPS but not exotoxin antigens, as well as endotoxin-like activity in boiled precipitates.