We previously reported that prostaglandin E2 (PGE2) at a physiologic concentration (10-8 M) and interferon gamma (IFNγ), 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 IFNγ-dependent effects on CD8+ cells by altering the number and/or affinity of their IFNγ receptors. CD8+ and CD4+ cells when cultured for 18 h expressed comparable numbers of IFNγ receptors of a single high affinity. Incubation with 10-8 M PGE2 for 18 h, however, increased the number of IFNγ 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 IFNγ-dependent suppressor cell differentiation, also did not affect IFNγ receptor expression on CD8+ cells. This observation of a specific stimulatory effect of PGE2 on the display of IFNγ receptors of CD8+ cells suggests a novel mechanism for eicosanoid function through tissue-specific regulation of hormone receptors.