This study was performed to test the hypothesis that responsiveness to the luteolytic action of estradiol is acquired as the luteal phase of the menstrual cycle progresses. The luteolytic effect of a fixed estradiol increment (270 ± 12 pg/ml serum) was assessed at different stages of luteal function in rhesus monkeys. A 4-day elevation in estradiol early in the luteal phase (days 2–6 after the LH peak) caused a decrease in the concentration of serum progesterone but did not shorten luteal life span. In contrast, when provided during the midluteal phase (days 6–10), the same 4-day estradiol increment promptly induced premature luteolysis. Furthermore, during sustained exposure to the estradiol increment from days 2–10, signs of premature luteolysis were not evident until day 7 after the LH peak. Thus, the effects of estradiol early in the luteal phase do not alter luteal life span; it is the effects after day 6 that precipitate luteolysis. These observations support the existence of a receptive period for the luteolytic action of estradiol in the rhesus monkey. (Endocrinology108: 1874, 1981)