To evaluate whether insulin-like growth factor-I (IGF-I) modulates neural activity in vivo, relative levels of brain [3H]2-deoxyglucose (2DG) uptake were compared in adult behaving and anesthetized wild type (wt) mice, and transgenic (Tg) mice with either brain IGF-I overexpression or ectopic brain expression of IGF binding protein-1 (IGFBP-1). Overall, awake behaving IGF-I Tg mice showed significant increases in brain 2DG uptake compared with wt and IGFBP-1 Tg mice. These differences were eliminated after anesthesia. 2DG uptake was similar in awake behaving, and anesthetized wt and IGFBP-1 Tg mice. Our observations thus suggest that IGF-I increases neural activity levels in vivo, and that it is not involved in regulating glucose consumption in the adult brain.