In order to determine whether effects of insulin on central nervous system (CNS) insulin-like growth factor II (IGF-II) content are direct or whether they are due to insulin-induced glucoprivation, short-term (2 h) time course studies were conducted utilizing the glucoprivic agent 2-deoxy-D-glucose (2-DG). Insulin (2 U/kg b.wt.), 2-DG (500 mg/kg b.wt.) or vehicle were administered to Sprague-Dawley rats (350-450 kg) and groups of animals were killed at time 0 and 15, 30, 45, 60, and 120 min following injection. Specific hypothalamic and hindbrain regions obtained by microdissection, were analyzed for IGF-II content by RIA. Insulin and 2-DG exerted similar effects on IGF-II content in the dorsomedial hypothalamus and the paraventricular nucleus. These data suggest that IGF-II was primarily regulated by glucoprivation in these regions. Only 2-DG altered ventromedial hypothalamic IGF-II content, and opposite responses to the two agents were observed in the arcuate nucleus. This uncoupling of IGF-II response suggests that differences in peripheral vs. central signals for IGF-II secretion may be involved. The vagal complex was responsive only to insulin injection indicating a specific response that may be tied to sensory vagal function.