Experiments were designed to test the hypothesis that LHRH receptors in the preoptic area (POA) are of physiological importance for maintaining estrous cyclicity in the rat. Bilateral cannulae were implanted just dorsal to the POA. Estrous cycles were monitored daily by vaginal smears. Antide, a long-acting LHRH antagonist, was infused bilaterally (2.5 micrograms/side) in the POA or the hypothalamus on the mornings of diestrus I and II. As controls, at separate times, rats also received similar infusions of either vehicle (1:1 water:propylene glycol) or a bombesin antagonist (#B0650; Sigma, St. Louis, MO). Collection of daily vaginal smears continued, and the number of days from the first infusion to the next day of estrus that preceded a normal cycle was recorded. After infusion of Antide into the POA, rats demonstrated varying durations of interrupted cycles ranging from 11 days to more than 100 days. These periods of disruption were characterized by either long periods of diestrus, long periods of estrus, or an extended period of diestrus followed by an extended period of estrus. After infusion of Antide into the dorsomedial, ventromedial, or anterior hypothalamic areas, rats had either a 4- or 5-day estrous cycle and continued to cycle normally. Likewise, infusions into the septum had no effect. Infusion of vehicle or bombesin antagonist into any of the hypothalamic or POA sites tested also resulted in no interruptions in the cyclic activity of the rats. Therefore, it appears that functional LHRH receptors in the POA are necessary to drive the normal estrous cycle.