To examine the possible pathophysiologic role of circulating immune complexes in patients with cystic fibrosis and other inflammatory lung diseases, we studied the reticuloendothelial clearance of IgG-sensitized autologous erythrocytes in 15 patients with cystic fibrosis, 6 with chronic obstructive lung disease not related to cystic fibrosis, 7 with immunodeficiencies, 5 with systemic lupus erythematosus, 4 who had previously undergone a splenectomy, and 10 normal subjects. Patients with chronic inflammation and recurrent infections (i.e., those with cystic fibrosis, chronic obstructive lung disease, and immunodeficiencies) had significantly faster clearance rates (P less than 0.05, less than 0.01, and less than 0.005, respectively) than normal subjects. In contrast, patients with systemic lupus erythematosus (a classic immune complex-mediated disease) and those who had undergone a splenectomy had delayed clearance. The accelerated reticuloendothelial clearance in patients with chronic inflammatory pulmonary disease associated with cystic fibrosis was similar to that observed in stimulated laboratory animals. The rapid clearance rate may account for the rareness of septicemia in such patients despite chronic, persistent local bacterial infection.