Lordosis behavior in ovariectomized guinea pigs is facilitated by the sequential action of estradiol-17 beta (E) and progesterone (P). The present study was designed to explore the possibility that administration of E in a pulsatile manner is more efficacious than a single injection of E with respect to lordosis facilitation in ovariectomized guinea pigs. The data indicate that pulse administration of unesterified E is more effective than a single large dose of E for the facilitation of lordosis behavior. Three injections of as little as 0.5 microgram E at 0, 19 and 28 hr followed by 0.5 mg P at 39 hr was more effective (63.6% responding with lordosis) than a single injection of as much as 15 micrograms E at hr 0 followed by vehicle injections at 19 and 28 hr and 0.5 mg P at 39 hr (0% responding). We also demonstrated that the 19 hr E injection could be eliminated and that two injections of E (0.5 microgram at hr 0 and 1.0 microgram at hr 28 followed by 0.5 mg P at hr 39) was at least as effective (69.0% responding) as three split injections in facilitating lordosis. This behaviorally effective pulse administration of E also resulted in significant induction of cytoplasmic progestin receptors in hypothalamic tissue. Further experiments indicated that a 28 hr interval between E pulses was optimal in terms of percent animals displaying lordosis. The data suggest that pulsatile E stimulation of brain tissues mediating lordosis is a highly effective mode of stimulation, and that an initial pulse of E sensitizes neural tissues to subsequent E administration.