The presence of glutamate/aspartate-like immunoreactivity was studied in normal human skin and in skin with gold-induced inflammation. In normal skin all epithelial cells were glutamate and, apparently more weakly, aspartate immunoreactive. Both glutamate and aspartate immunoreactivities were also found in macrophage-like, HLA-DR positive cells in the dermis and in the epidermis. The intensity of glutamate and especially aspartate-like immunoreactivities seemed to be increased in the epidermis and dermis of the inflamed as compared to the normal skin, and this increase was particularly pronounced in the HLA-DR positive (dendritic) cells in the epidermis. Numerous cells, often of the mononuclear type, in the superficial dermis expressed glutamate- and aspartate-like immunoreactivities in the inflamed skin and many of these were HLA-DR positive. The functional role of glutamate and aspartate in normal skin, and the significance of the increase in the levels of these amino acids in several cell populations in the inflammatory skin is not known, but modulatory or protective roles may be considered. High concentrations of these amino acids could also induce cell damage. Moreover, the macrophage-like cells in the human skin may have a role in the processing of glutamate and aspartate on a recycling basis.