In order to evaluate the role of changing pituitary responsiveness to LRF in mediating the midcycle ovulatory LH surge in rats, LH secretory response to LRF was determined at different times during the estrous cycle. A standard dose of crude methanol extract of porcine stalk median eminence tissue (SME) was used as a source of LRF and responses were evaluated by LH radioimmunoassay in plasma removed before and ten minutes after intravenous injection. A significant response was elicited on all days of the estrous cycle. Responses early in proestrus and estrus were moderately but significantly greater than those observed at diestrus. Striking effects were noted in the late afternoon of proestrus at the time of the ovulatory LH surge. Pentobarbital blockade of the ovulatory surge early in the afternoon of proestrus prevented the sensitization of the pituitary which is observed in unblocked animals. Since estrogen secretion is known to be maximal late in diestrus and early in proestrus, failure to demonstrate more than minimal increases in pituitary responsiveness at these times in blocke animals indicates that direct effects of preovulatory estrogen secretion on the pituitary is not alone responsible for the cyclic changes in pituitary sensitivity which occur at proestrus. Progesterone secretion probably can be discounted as a cause of pituitary sensitization in proestrus since work by others has shown that this steroid inhibits responses to LRF. On the basis of these considerations it is proposed that the increased sensitivity of the pituitary to exogenous LRF at midcycle is due to endogenous LRF secretion or other hypothalamic factors in turn stimulated by preovulatory estrogen secretion. (Endocrinology94: 974, 1974)