In several mammalian species, prostaglandin F2 alpha (PGF2 alpha) released from the uterus causes corpus luteum regression, and thereby regulates the length of the oestrous cycle or pseudopregnancy. If the animal becomes pregnant, luteal regression must be prevented since ovarian progesterone is necessary for pregnancy maintenance during at least the first one-third of pregnancy. Evidence is presented that the guinea-pig conceptus produces an antiluteolytic factor which suppresses PGF2 alpha output from the uterus by preventing the increase in uterine PGF2 alpha-synthesizing capacity which occurs around the time of luteolysis. Experiments in unilaterally pregnant guinea-pigs, with either an intact or a transected sterile horn, indicate that this factor acts both locally systemically, though separation of the two uterine horns does greatly reduce its effect on the sterile side. Oestradiol administered during early pregnancy induces abortion, which is associated with a high PGF2 alpha-synthesizing capacity of the uterus. However, luteal regression does not take place while the conceptuses are in the uterus. Spontaneously aborting guinea-pigs behave similarly. The conceptus may therefore secrete a luteotrophic hormone as well. Luteal maintenance during early pregnancy in other species is discussed, since experiments on sheep indicate that the sheep embryo may also secrete an antiluteolytic factor.