The morphological distribution of quinolinic acid phosphoribosyltransferase (QPRT), the degradative enzyme of the endogenous excitotoxin quinolinic acid, was studied in the human hippocampal formation and parahippocampal gyrus by immunohistochemical techniques. In seven neurologically normal human brains obtained at autopsy, QPRT - immunoreactivity (QPRT-i) was found in both glial cells and neurons. Glial cells exhibiting QPRT-i, sharing the morphological features of astrocytes, were observed in all hippocampal subfields. The polymorphic layer of the dentate gyrus contained the highest density of QPRT-i glial cells. Numerous QPRT-i glial cells were also found along both sides of the fused hippocampal fissure and in the white matter including the alveus of Ammon's horn, whereas only a few were observed in the granule cell layer and the stratum pyramidale. Neurons containing QPRT-i were found mainly in the subiculum and in the strata oriens and pyramidale of CA1. They were mostly small and polymorphic or fusiform, thus indicating that they may belong to a subpopulation of interneurons. Moderate numbers of QPRT-i glial cells and neurons were also observed throughout layers II-VI of parahippocampal cortex. The localization of QPRT-i in selected glial cells and neurons suggests that in the regions examined these cellular elements might play specific roles in the regulation of quinolinic acid function.