The hormone-like substance prostaglandin (PG)E was studied to evaluated its effect on various elements of the immune system both in vitro and in vivo under normal and tumored conditions. When interferon-activated mouse macrophages are incubated with mouse lymphoblastic leukemia cells in vitro exogenously added PGE inhibited the tumoricidal activity of these activated macrophages. The activated macrophages release high concentrations of PGE and in this way the PGE could act locally in negative feedback inhibition to limit cell activities and consequently cell growth. The in vitro effect of PGE was studied to determine its effect on the in vitro blastogenesis of thymic and splenic T and B lymphocytes from normal and tumored mice. It was found that PGE stimulated splenic and thymic lymphocytes from tumored mice. The effect of exogenously added PGE was also studied to determine its effect on the in vivo delayed hypersensitivity reaction of normal or tumored mice. PGE cause a stimulation over the control values of normal mice as detected by the footpad swelling assay. However, PGE was found to significantly inhibit the delayed hypersensitivity reaction of tumored mice.