We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9Ϯ20.2 mg/l and 203.2Ϯ31.1 mg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3Ϯ19.5 mg/l and 204.6Ϯ21.0 mg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3Ϯ61.0 mg/l and 167.6Ϯ22.7 mg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3Ϯ79.0 mg/l, P<0.025 and 532.0Ϯ85.9 mg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1,25-dihydroxyvitamin D (1,25-(OH) 2 D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH) 2 D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1a hydroxylase in tuberculous pleuritis.