To study the mechanism by which estradiol induces a preovulatory surge of follicle stimulating hormone (FSH), we concluded experiments designed to determine: (1) the time course of change in luteinizing hormone releasing hormone (LHRH)-induced FSH release after estradiol in vivo, and (2) whether LHRH is required to trigger the FSH surge. Steers were given 1 microgram LHRH at 20-min intervals for 10 h, beginning 2, 8, 12 or 20 h after estradiol. During this period, serum samples were collected every 2 h (just before every sixth injection). The magnitude of LHRH-induced FSH release from baseline to peak was 40 ng/ml in oil-treated controls and increased (P less than .05) to 77 ng/ml when estradiol was given 2 h earlier. When LHRH was given starting at 8, 12 or 20 h after estradiol, the FSH response to LHRH was further augmented (P less than .001) so that the increment from baseline was about 150 ng/ml. To determine whether estradiol alters LHRH-induced FSH release in ovariectomized (ovx) cows as it does in steers, we gave ovx cows 1 microgram LHRH every 20 min beginning 2 or 8 h after estradiol. Serum samples were collected every 80 min (just before every fourth injection). When LHRH treatment began 2 h after estradiol, LHRH-induced FSH release was blocked (P less than .025) at 80 min after LHRH, but increased thereafter. When LHRH was given starting at 8 h after estradiol, concentrations of FSH increased 156 ng/ml above baseline. This release of FSH exceeded (P less than .001) the comparable value for cows given LHRH after oil (37 ng/ml). Furthermore, the LHRH-induced FSH release initiated 8 h after estradiol resembled the preovulatory and estradiol-induced FSH surges in magnitude (greater than 180 ng/ml), duration (8 to 10 h) and general shape. These results demonstrate that estradiol initially inhibits, then augments the capacity of the pituitary to secrete FSH in response to LHRH stimuli. The pituitary attains peak sensitivity long before the expected surge. Thus, we hypothesize that increased LHRH secretion triggers the FSH surge.