Insulin-like growth factor I (IGF-I) is a major regulator of bone growth during childhood. However, beyond knowledge that IGF-I influences longitudinal growth, its associations to changes in the cross-sectional dimensions, the volume, or the material density of bone during growth are unknown. We assessed the relationships between serum IGF-I and measurements of cross-sectional area, cortical bone area, and cortical bone density at the midshaft of the femur in 197 normal healthy white children and adolescents (103 boys and 94 girls; aged 7.8-18.2 yr). Bone determinations were obtained using computed tomography, and levels of IGF-I were measured by RIA after an extraction procedure. IGF-I correlated significantly with both cross-sectional area (r = 0.49; P < 0.0001) and cortical bone area (r = 0.50; P < 0.0001), but did not correlate with the material density of cortical bone (r = -0.08). Multiple regression analyses showed that circulating levels of IGF-I were associated with cross-sectional area (P = 0.03) and cortical bone area (P = 0.04) values, even after correcting for the confounding effects of age, gender, weight, and femoral length. We conclude that IGF-I is a major determinant of the cross-sectional properties of bone, but does not influence the material density of bone, in the appendicular skeleton.