The immunosuppressive effects of MPA (medroxyprogesterone acetate) were tested in clinical studies with laboratory dogs and rabbits. The laboratory procedures employed in the studies are explained and results are tabulated and graphed. 2 microscopic photographs illustrate the observed effects. MPA significantly prolonged the survival of dogs with renal allografts. MPA was shown to enhance the immunosuppressive activity of azathioprine in dogs with renal allografts. In rabbits, MPA extended survival of rabbit skin allografts and suppressed the primary humoral antibody response. The influence of MPA on circulating leukocytes and on the histology of lymph nodes, spleen, thymus, liver, and kidney was also assessed. MPA is probably not as potent an immunosuppressive agent as azathioprine or corticosteroids. It is, however, useful in humans due to its low toxicity. It is possible that high local progesterone levels in the fetus and placenta during pregnancy help to prevent fetal rejection.