Interleukin-1 (IL-1) has a broad range of effects on physiologic processes, including immunologic phenomena. In maintaining the tissue homeostasis the existence of feed-back mechanisms regulating down the IL-1 activity would be beneficial for the host. We and other investigators have provided evidence that such a regulatory circuit exists and may be altered by agents such as glucocorticoids and as well as by the UV irradiation. Here we provide evidence describing the mode of action of an accessory cell derived inhibitor of the IL-1 activity. This inhibitor is a product of radioresistant cells, it does not represent a nonspecific inhibitor of the DNA synthesis and appears to be specific for IL-1 since it does not interfere with the IL-2 dependent T cell proliferation. It affects both the IL-2 production and the induction of IL-2 receptor expression. As indicated in our previous work the immunoinhibitory factors affecting T cell proliferation are present in the sera of patients suffering from chronic renal and hepatic diseases. Further analyses have shown that these serum inhibitors have the same mode of action as macrophagederived glucocorticoid-induced inhibitors. Thus, it appears that the production of an IL-1 receptor antagonist may be enhanced in a pathological condition and during chronic inflammations in particular. Its significance for the disease pathogenesis remains to be elucidated.