A high affinity antiprogesterone antibody (APA) was tested in both pseudopregnant and pregnant rats for its ability to alter serum and ovarian concentrations of total and free progesterone and serum gonadotropins and for contragestational effects. APA injected ip on the sixth day of pseudopregnancy resulted in rapidly increased levels of total progesterone in serum, but no detectable change in free progesterone as measured by equilibrium dialysis. Serum gonadotropins similarly increased after APA injection. Progesterone concentrations in various body tissues indicated an initial increase in progesterone production followed by a marked decrease apparently in response to induce luteolysis. Similar levels of hormones were obtained in pregnant rats after ip administration of APA on day 10 of gestation. Fetal resorption followed in all animals and was complete within 96 h. The effect of APA on fetal loss appears to be a combination of a direct reduction of uteroovarian progesterone concentration and a negative feedback of progesterone on the pituitary release of gonadotropins, thus resulting in luteolysis and a further reduction in available progesterone.