When estradiol is administered to the ewe after day 8 of the estrous cycle, corpora lutea (CL) regress prematurely. The following results suggest that a period of progestational influence on the ewe facilitates the luteolytic effect of estradiol. (1) When progesterone was administered on days 1 to 4, the injection of estradiol as early as days 5 and 6 caused premature luteal regression. (2) The injection of estradiol on days 1 to 8 prevented estradiol administered on days 9 and 10 from causing luteal regression; however, the withholding of estradiol injections from day 5 through 8, when endogenous progesterone secretion is increasing, allowed estradiol given on days 9 and 10 to cause premature luteolysis. (3) When estradiol was injected on days 1 to 8 and exogenous progesterone was superimposed on days 5 to 8, estradiol injected on days 9 and 10 caused luteal regression.