In addition to the excitatory role played by the amino acid transmitters glutamate and aspartate in the central nervous system, their sulfur-containing analogues homocysteic acid (HCA) and cysteine sulfinic acid (CSA) may also play a similar role. HCA is released and taken up by rat CNS tissue; it excites neurons predominantly via NMDA receptors whenever present, and is neurotoxic. The pattern of HCA-like immunoreactivity in the rat indicates a localization of HCA mostly in glial elements, although its presence in nerve terminals and neuronal perikarya cannot be excluded. In the cerebellum of newborn and adult animals, the Bergmann glial cells and the astrocyte endfeet are immunoreactive, either in the presence or in the absence of climbing fibers. In the cortex, hippocampus, and retina, labeling is seen in both glial and neuronal elements. Excitatory signaling involving glial elements is discussed.