The excitotoxic brain metabolite quinolinic acid has been hypothetically linked to the pathogenesis of neurodegenerative disorders. By using antibodies prepared against a homogeneous preparation of its catabolic enzyme, quinolinic acid phosphoribosyltransferase [QPRTase; nicotinate-nucleotide:pyrophosphate phosphoribosyltransferase (carboxylating), EC 2.4.2.19], immunocytochemical methods were applied to assess the cellular and subcellular localization of quinolinic acid in the rat brain. On the light-microscopic level, the enzyme was found to be preferentially associated with glial elements of variable morphology. In addition to its presence in glial cells, QPRTase was contained in tanycytes and ependymal cells of the cerebral ventricles and, sporadically, in neurons. Overall, QPRTase immunoreactivity was noted in every brain region studied, the histological pattern being in good accordance with the regional variation of enzyme activity established in biochemical studies. As judged on the ultrastructural level, QPRTase, in all cell types examined so far, was often noted in densely stained roundish cytoplasmic bodies (0.1-0.8 micron in diameter), which were bounded by a single membrane. In functional terms, these structures may represent early lysosomes, secretory granules, or residual bodies. The particular anatomical arrangement of the quinolinic acid system may reflect the brain's defense strategy against detrimental effects of the endogenous excitotoxin.