We previously found that bilateral lesions of the suprachiasmatic nucleus abolished hyperglycemic response to intracranial injection of 2-deoxy-D-glucose in rats. Because the hyperglycemia due to 2-deoxy-D-glucose was shown to be dependent on the functions of the adrenal medulla and sympathetic nervous system, the effect of bilateral lesions of the suprachiasmatic nucleus on changes in the nervous activity of sympathetic efferents to the adrenal after intracranial injection of 2-deoxy-D-glucose was examined in rats. It was found that bilateral lesions of the nucleus eliminated the increase in neural activity of the sympathetic efferent that occurred after the injection of 2-deoxy-D-glucose. Because the suprachiasmatic nucleus possesses neurons containing a vasoactive intestinal polypeptide-like substance, the effects of vasoactive intestinal polypeptide and 2-deoxy-D-glucose, administered alone or in combination, on the sympathetic activity were examined in intact control rats and in rats with bilateral lesions of the suprachiasmatic nucleus. It was found that in the normal control rats, vasoactive intestinal polypeptide alone increased the sympathetic activity, whereas it dramatically enhanced the sympathetic response to 2-deoxy-D-glucose. However, in rats with bilateral lesions of the suprachiasmatic nucleus, vasoactive intestinal polypeptide alone elicited no increase in the nervous activity of the sympathetic efferents to the adrenal, but combined administration of vasoactive intestinal polypeptide and 2-deoxy-D-glucose caused an increase in the nervous activity of sympathetic efferents to the adrenal. These findings suggest that the suprachiasmatic nucleus is involved in the enhancement of sympathetic activity caused by intracranial injection of 2-deoxy-D-glucose, and that neurons containing a vasoactive intestinal polypeptide-like substance in the suprachiasmatic nucleus play an important role in the sympathetic enhancement that occurs after intracranial injection of 2-deoxy-D-glucose. This role might be a permissive and facilitative one.