The regulation of blood glucose is a complex process involving the integration of the CNS with both hormonal and neural mechanisms. Although neuropeptide participation in the process is only partly understood at present, several conclusions are evident. First, neuropeptides are present in various portions of the autonomic nervous system from the central components in the hypothalamus to the peripheral ganglia and the adrenal medulla. Their mediation of neural impulses involved with glucoregulation is unquestionable, though their interaction with monoaminergic neuro-transmitters requires further study. Second, many of these peptides are also present in the gastrointestinal tract and the endocrine pancreas. The results of studies involving the systemic administration of the various peptides and the measurement of their endogenous circulating levels indicate that their effects are produced not by a classical hormonal mechanisms--i.e. secretion into the blood stream--but by direct cell to cell (paracrine) actions or neurotransmitter actions in the pancreas, adrenal medulla, and liver. Third, a pattern is beginning to emerge in which specific neuropeptides appear to exert an integrative role in a specific homeostatic system at different anatomic locations. For example, somatostatin is involved in glucose absorption from the gastrointestinal tract, in pancreatic hormone secretion, and in hepatic glucose production, and somatostatin secretion from the hypothalamus is stimulated by glucopenia. Whether these actions are interrelated through a CNS control mechanism or represent evolutionary developments from a single neuropeptide-mediated process in a more primitive species remains to be elucidated. In either case, a fuller understanding of the role of neuropeptides in glucoregulation should provide new insights into disorders of carbohydrate metabolism.