W e previously reported that prostaglandin E2 (PGE2) at a physiologic concentration (10(-8) M) and interferon gamma (IFN gamma), acting sequentially, were required for the differentiation of suppressor cells in mitogen-stimulated cultures. The present study was designed to test whether PGE2 might mediate IFN gamma-dependent effects on CD8+ cells by altering the number and/or affinity of their IFN gamma receptors. CD8+ and CD4+ cells when cultured for 18 h expressed comparable numbers of IFN gamma receptors of a single high affinity. Incubation with 10(-8) M PGE2 for 18 h, however, increased the number of IFN gamma receptors on CD8+ cells without affecting the binding affinity. Similar effects were not observed with CD4+ cells, nor when CD8+ cells were cultured in 10(-8) M PGD2. Concentrations of PGE2, which were ineffective in the induction of IFN gamma-dependent suppressor cell differentiation, also did not affect IFN gamma receptor expression on CD8+ cells. This observation of a specific stimulatory effect of PGE2 on the display of IFN gamma receptors of CD8+ cells suggests a novel mechanism for eicosanoid function through tissue-specific regulation of hormone receptors.