According to the endotoxin lipoprotein hypothesis, lipoproteins may down-regulate cytokine production by neutralizing lipopolysaccharide (LPS) binding protein (LBP) complexes. We investigated the correlation between lipoproteins, LBP, cytokine production, and clinical status in Delta F 508 (homozygous) individuals. Cystic fibrosis patients with mild disease were compared with those with more severe disease and age-matched controls. LBP, IL-8, and tumor necrosis factor-alpha, using a chemiluminescent immunometric assay, and fat intake, as well as serum triglycerides, cholesterol, very low density lipoprotein, LDL, and HDL were measured. In more severe disease there was a correlation between maximum expiratory flow at 25% of vital capacity and HDL. To adjust for the influence of colonization with Pseudomonas aeruginosa, those who were colonized with P. aeruginosa were analyzed separately. There was a significant correlation between LBP and forced expiratory volume in 1 s. Lipoproteins may have a modulating effect in more advanced disease and are not influenced by fat intake. LBP correlates those who were colonized with P. aeruginosa (Psa+) with clinical status as well as lung function and may be a critical molecule regulating LPS-induced inflammation.