Cell culture experiments with approximately physiological amino-acid concentrations show that a 3- to 5-fold elevation of the extracellular glutamate concentration causes a substantial decrease of the intracellular cysteine and glutathione content of murine peritoneal macrophages. Our experiments show, moreover, that murine peritoneal macrophages, human peripheral blood monocytes, and murine fibroblastoid cells (L-cells) consume cystine and release cysteine into the extracellular space. This process was found to be markedly suppressed in all three cell types by a 3- to 5-fold increase of the extracellular glutamate concentration. Possible implications of these effects for the pathogenetic mechanism of the acquired immunodeficiency syndrome (AIDS) are discussed.