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The effects of all-trans-retinoic acid were investigated on the immune responses in C57Bl/6 mice after daily oral administration for one week. In selected experiments the immunosuppressive chemicals, cyclophosphamide and cyclosporin A were used in conjunction with retinoic acid. Retinoic acid stimulated the production of antibodies against sheep red blood cells and DNP-Ficoll; however, retinoic acid did not reverse the depression caused by immunosuppressive chemicals. In non-immunized animals retinoic acid stimulated the production of IL-1 but not of IL-2. The mitogenic responses of splenocytes against concanavalin A, phytohemagglutinin and pokeweed mitogen were depressed after the retinoic acid treatment; those against lipopolysaccharide were not influenced. Treatment with retinoic acid did not alter the mixed leukocyte responses but increased the activity of NK cells. Results indicate that retinoic acid may act as an adjuvant via activating macrophages, however, retinoic acid cannot reverse the immunosuppression induced by potent chemicals.