A potent synthetic progestin, medroxyprogesterone acetate (MPG), was evaluated for immunosuppressive activity. The survival of dogs with renal allografts was significantly prolonged and serum creatinine was decreased in animals treated with large doses of MPG. Survival of dogs with renal allografts which received both medroxyprogesterone and azathioprine was markedly prolonged when compared with animals receiving azathioprine alone. In rabbits receiving MPG alone, skin allografts survived 1.7 to 2. 8 times longer than controls. The primary humoral antibody response of rabbits to bovine y-globulin was also suppressed. The influence of MPG on peripheral leukocyte count and the histology of lymph nodes, spleen, and thymus was studied in dogs. Although probably not as potent an immunosuppressive agent as azathioprine or corticosteroids, MPG may be useful in humans because of its low toxicity.