Intracranial self-stimulation of the lateral hypothalamus of the rat was markedly increased by d-amphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same animals from the medial frontal cortex were unaffected by food deprivation and only slightly increased by d-amphetamine administration. Furthermore, a large difference between d-vs. Z-amphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. The results of this study were consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus.