This study evaluates the effects of synthetic progestational agents on immune responses. Adult white rabbits weighing between 3 and 4 kg were surgically castrated. 5 rabbits were given a steroid 1 week later in a dose 5 times the upper limit of its human therapeutic dose. 4 mEq of potassium chloride solution were administered intraperitoneally each in cortisone-treated animals. Control groups included castrated and noncastrated animals, and those receiving propylene glycol or oil alone. Allograft exchanges were performed after at least 1 week of steroid administration. No control allograft was rejected. Normal and castrated animals had an average rejection time of 9 days. Cortisone-treated animals tolerated their allografts for at least 3 weeks. Graft survival was unaffected by estradiol and progesterone, synthetic progestins, 17-hydroxyprogesterone caproate and medroxyprogesterone acetate. Allograft survival was significantly prolonged to an average of 13 days by norethindrone and norethynodrel compounds of the "19 nor" group of synthetic progestational agents. A series of analyses of variance using the 'F' test between the castrated group and those receiving progesterone, medroxyprogesterone and cortisone indicated that these compounds significantly reduced circulating antibody production. There was no difference in the response of animals receiving medroxyprogesterone and those receiving cortisone. The findings show that the mechanisms of graft rejection and antibody production are sufficiently distinct to be inhibited by different steroids in different degrees. Further research should be done to determine the effects of these progestational agents on immune responses in humans.