To investigate cortical bone composition and the role of the insulin-like growth factor (IGF) system in active acromegaly, iliac crest bone biopsies were obtained from 15 patients (3 women and 12 men), aged 21-64 yr (mean, 45.6 yr), and 25 age- and sex-matched controls (8 women and 17 men), aged 22-66 yr (mean, 44.6 yr). Levels of IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), IGFBP-5, and total protein were determined in extracts obtained after ethylenediamine tetraacetate and guanidine hydrochloride extraction. Osteocalcin and calcium were determined in extracts after HCl hydrolysis. Cortical bone contents of IGF-I, IGF-II, and IGFBP-5 were significantly elevated in the acromegalic patients compared with control values [91% (P < 0.001), 44% (P < 0.04), and 115% (P < 0.004), respectively]. There was no significant difference in IGFBP-3, osteocalcin, protein, and calcium between patients and controls. This study suggests that the increased levels of growth factors in cortical bone from acromegalics is a reflection of local production, secondary to a chronic systemic excess of GH and IGF-I.