Zinc (Zn) deficiency can result in severe growth retardation in mammals, and in a number of animal model systems it leads to low circulating insulin-like growth factor-I (IGF-I) concentrations. Using a weanling male rat model and a number of feeding schemes, we show that in addition to lower circulating IGF-I concentrations, Zn deficiency leads to alterations in the distribution of serum IGF-binding proteins (IGFBPs). Serum from Zn-deficient animals labeled in vitro with [125I]IGF-I displayed three peaks of tracer activity: 150 kd (IGFBP-3), 37 kd (IGFBP-2 and -1), and 8 kd (free [125I]IGF-I). Relative to controls, Zn-deficient animals demonstrated more tracer binding in the 37-kd region, whereas less was found in the 150- and 8-kd peaks. Serum from chronically calorie-restricted fed animals displayed [125I]IGF-I binding profiles similar to Zn-deficient serum, implicating Zn deficiency-induced anorexia as the principle factor underlying both the lower circulating IGF-I and the alterations in IGFBP profiles. Concentrations of IGFBP-4 were unaffected by diet manipulation based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/Western ligand blot (WLB) analysis.