Intracranial sefl-stimulation (ICSS) was studied in rats with chronically implanted lateral hypothalamic, substantia nigra, or medial frontal cortex bipolar electrodes. A comparison of the effects of d- and l-amphetamine on ICSS response rate indicated that the d isomer had a greater facilitatory effect than the l isomer at lateral hypothalamic and substantia nigra electrode sites but that neither isomer significantly affected medial frontal cortex ICSS. d-Amphetamine resulted in a dose-related increase in motor activity, but the same doses of the l isomer resulted in decreased motor activity. Only lateral hypothalamic ICSS response rates increased significantly in response to food deprivation. Increases in current intensity above the level used for amphetamine and food-deprivation testing facilitated lateral hypothalamic and substantia nigra ICSS response rates but did not significantly affect medial frontal cortex response rates. The responsiveness of ICSS at each electrode site appeared to be correlated with the fiber- and cell-body densities of catecholaminergic systems in the brain.