The goal of this study was to characterize the respective effects of aging and endurance training on serum insulin-like growth factor I (IGF-I), as well as IGF-binding proteins (IGFBP)-1 and -3 in relationship with glucose disposal. Thirty-two subjects (16 middle-aged men: 8 cyclists and 8 sedentary men; and 16 young men: 8 cyclists and 8 sedentary men) were compared in this study. Insulin sensitivity (SI) and glucose effectiveness (Sg) were assessed by the minimal model. Endurance training increased SI, Sg, and IGFBP-1 and -3 in both age groups (P<.05), but the older group showed a greater increase in SI and IGFBP-1 than the younger group (P<.05). IGF-I was increased only in the middle-aged trained men (P<.05). An effect of aging was found in the sedentary subjects, who presented lower IGF-I and SI (P<.05) when older. This effect disappeared with training since IGF-I and SI were nearly identical in young and middle-aged trained subjects. SI was correlated with IGFBP-1 (P<.01). These data suggest that (1) endurance training increases SI, Sg, and IGFBP-1 and -3 in men and, for SI and IGFBP-1, this increase becomes more pronounced with age; (2) endurance training may attenuate the aged-related decline in SI and IGF-I; and (3) IGFBP-1 may protect against the risk of hypoglycemia by counteracting the hypoglycemic effect of IGF-I in such situations of high SI.