Deflazacort is a synthetic glucocorticoid with fewer adverse effects on bone and carbohydrate metabolism than prednisone or beta-methasone. Its antiinflammatory effects have compared favorably to prednisone in European studies of rheumatoid arthritis. We compared the immune effects of prednisone and deflazacort in normal volunteers. Circulating lymphocytes were reduced similarly by equivalent doses of both drugs; monocyte numbers were reduced more by deflazacort. Each drug suppressed autologous mixed lymphocyte reaction in vitro and in vivo; this effect persisted longer with deflazacort. Deflazacort may be a superior therapeutic agent because of its lower toxicity and longer duration of one immunosuppressive effect; it might be effective in alternate day regimens.