Normal peripheral blood mononuclear cells (PBMC) were primed with sera from 22 predialytic uremic patients, normal sera, concanavalin A, or both. Their suppressive activity was subsequently tested on fresh phytohemagglutinin-stimulated allogeneic responders (i.e., genetically unrelated to either primed cell or sera donors). Uremic serum induced suppressor cell activity in the normal PBMC. No correlation was found between serum urea/creatinine levels and their effects on suppressor cell activity. The induced activity, expressed as percent suppression, was similar to that induced by concanavalin A. In PBMC primed with both concanavalin A and uremic serum, an additive suppressive effect was evident. The suppressor subset(s) induced by uremic serum proved to belong to adherent cell population. Addition of indomethacin or catalase to responder systems did not abolish the suppressive effects, thus suggesting a mechanism of action other than prostaglandin or hydrogen peroxide release.