OBJECTIVE The aim of this investigation was to characterize the GH–IGF axis of patients with AIDS associated wasting. A special emphasis was placed on determining whether IGF binding proteins (IGFBPs) of patients who have lost more than 10% of their ideal body mass are structurally different from the IGFBPs of patients with no weight loss.DESIGN AND PATIENTS A cross‐sectional study of 11 AIDS patients was performed to determine whether the IGF system is abnormal in AIDS patients with wasting. Seven additional AIDS patients were followed longitudinally to determine whether AIDS patients experience long‐term changes to their IGF system.MEASUREMENTS Serum levels of GH and IGF‐I were measured by radioimmunoassay, IGF‐II was measured by radioreceptor assay, and IGFBP‐1 was measured by an enzyme linked immunoassay. IGFBP‐3 and IGFBP‐3 protease activity were measured by ligand blotting and a BP‐3 protease assay, respectively. IGFBP‐3 ternary complex formation and IGFBP‐1 phosphovariants were analysed by non‐denaturing PAGE.RESULTS AIDS patients who had lost more than 10% of their ideal body mass demonstrated a 55% reduction in serum IGF‐I (81vs179 μg/l) and a 70% reduction in IGF‐II (226vs776 μg/l), compared to healthy HIV negative subjects. IGF‐I levels were depressed, in some patients, despite high serum levels of GH. AIDS patients who had lost more than 10% of their ideal body mass had low levels of IGFBP‐3 and a reduced ability to form the IGFBP‐3 ternary complex. The IGFBP‐3 ternary complex could be restored only upon addition of pure IGFBP‐3 and acid labile subunit to serum. Serum IGFBP‐1 was increased more than threefold compared to control subjects (90vs24 μg/l). IGFBP‐1 was present as a free phosphoprotein in AIDS patients with low levels of IGF‐I and in a bound form when serum IGF‐I levels were normal. Changes in the GH–IGF axis were sustained for up to 25 months in AIDS patients with wasting.CONCLUSIONS AIDS wasting is associated with a GH resistant state that results in low levels of serum IGF‐I, IGF‐II and IGFBP‐3, elevated levels of phosphory