Prostaglandins are important modulators of inflammation and of humoral and cellular immune responses1-8. In order to evaluate a possible mechanism for the regulation of immune responses we have studied the effects of prostaglandins on the expression of I-region-associated (Ia) antigens by macrophages. The expression of these glycoproteins is essential for macrophages to function as antigen-presenting cells during the induction of immune responses9. The synthesis and membrane expression of Ia, however, is not a constitutive property of the phagocyte10 but is under regulation and a positive regulation of this process is exhibited by activated T cells11. In contrast, a negative regulation is conspicuously found in the neonate where a product from a young replicating macrophage inhibits the expression of Ia by the mature macrophages12. We show here that prostaglandins of the E series (PGE) are potent inhibitors of the expression of Ia-antigens on macrophages and that thromboxane B2 (TXB2) antagonizes the effect of PGE.