Effects of antibodies to progesterone on early pregnancy were studied in rabbits. A total of 124 rabbits were employed to determine the effects of active immunization with progesterone-11alpha hemisuccinate couple to bovine serum albumin (P-BSA) on progesterone-dependent responses. P-BSA was administered by multiple intradermal injections in complete Freund's adjuvant. The rabbits were bled immediately after mating to obtain an estimate of the levels of antibodies to progesterone (anti-P) and were sacrificed 1.25, 3, 5, 6, 7, or 12 days later. Immunization with P-BSA did not cause marked changes in the numbers of corpora lutea, fertilization rate or the weights of corpora lutea, adrenal glands and ovaries. Mean serum progesterone levels in rabbits immunized with P-BSA were 8-15 times higher than controls on Days 3, 5, and 7 of pregnancy. There was a highly significant positive correlation (r=.85, p less than .01) between levels of anti-P at the time of mating and serum progesterone at necropsy. The elevation in serum progesterone and the correlation with the anti-P levels were not markedly affected by replacement therapy with medroxyprogesterone acetate (MPA). In P-BSA-immunized rabbits uterine weights were significantly lower than controls (p=.05 or less than .01). Inhibition of the progestational response of the uterus in the presence of markedly elevated serum progesterone levels indicates that progesterone bound to antibody was not readily available to target organ cells. Progestational changes in the uteri of P-BSA-immunized rabbits were delayed as compared to controls. Embryo survival in the immunized rabbits was lower (p less than .01) at Days 5, 6, 7, and 12 and embryo diameters were lower (p less than .01) at Days 5, 6 and 7 of pregnancy. Embryo survival rates and diameters at Day 5, 6, and 7 were both negatively correlated (p less than .05) with the levels of anti-P at the time of mating. The detrimental effects of P-Basa immunization on progesterone-dependent responses were completely or partially blocked by MPA.