. Differential responses of IGF-I molecular complexes to military operational field training. J Appl Physiol 95: 1083-1089, 2003; 10.1152/japplphysiol. 01148.2002.-Insulin-like growth factor (IGF) I and IGF binding proteins (IGFBPs) modulate metabolic activity and tissue repair and are influenced by nutritional status. IGF-I circulates in free, ternary [IGF-I ϩ IGFBP-3 ϩ acid labile subunit (ALS)], and binary (IGF-I ϩ IGFBP) molecular complexes, and the relative proportions regulate IGF-I extravascular shifting and bioavailability. This study examined the hypothesis that sustained physical activity and sleep deprivation superimposed on a short-term energy deficit would alter the IGFBP concentrations and alter the proportions of IGF-I circulating in ternary vs. binary molecular complexes. Components of the IGF-I system (total and free IGF-I; IGFBP-1, -3, and ALS; nonternary IGF-I and IGFBP-3), biomarkers of metabolic and nutritional status (transferrin, ferritin, prealbumin, glucose, free fatty acids, glycerol, -hydroxybutyrate), and body composition were measured in 12 men (22 Ϯ 3 yr, 87 Ϯ 8 kg, 183 Ϯ 7 cm, 20 Ϯ 5% body fat) on days 1, 3, and 4 during a control and experimental (Exp) period. During Exp, subjects performed prolonged work (energy expenditure of ϳ4,500 kcal/day) with caloric (1,600 kcal/day) and sleep (6.2 h total) restriction. IGF-I and IGFBP-3 were measured by immunoassay before and after immunoaffinity depletion of ALS-based complexes (i.e., ternary complex removal). Exp produced losses in body mass (Ϫ3.0%), lowered total IGF-I (Ϫ24%), free IGF-I (Ϫ42%), IGFBP-3 (Ϫ6%), nonternary IGF-I (Ϫ27%), and IGFBP-3 (Ϫ16%), and increased IGFBP-1 (256%). No Exp effects were observed for ALS. No changes were observed in the proportion of IGF-I circulating in free (ϳ1.2%), ternary (ϳ87.4%), or nonternary (ϳ11.4%) molecular complexes. During Exp, glucose concentrations were lower on day 3, but days 1 and 4 were statistically similar. In conclusion, during a short-term energy deficit in young, healthy men, 1) IGF-I system components differentially respond (both in direction and magnitude) to a given metabolic perturbation and 2) the relative proportion of IGF-I sequestered in ternary vs. nonternary molecular complexes appears to be well maintained.