It is well known that electrolytic lesions in the medial preoptic area (MPOA) and the lateral hypothalamic area (LHA) seriously impair masculine sexual behavior in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO), in the MPOA were as effective as electrolytic lesions in eliminating copulation whereas no behavioral effects were detected following similar infusions in the LHA. Histological examination of MPOA and LHA following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Also, immunohistochemical studies suggested that the serotonergic innervation of the MPOA remained largely intact in spite of IBO treatment; similarly, the damage inflicted by IBO in LHA on tyrosine hydroxylase-immunoreactive fibers in the medial forebrain bundle was insignificant. These data suggest that: (i) the functional integrity of MPOA nerve cell bodies is necessary for the expression of sexual behavior, and (ii) disruption of mating produced by electrolytic LHA lesions is due to disruption of medial forebrain bundle fiber systems. Behavioral observations of non-copulating males suggested that the MPOA injury did not interfere with all aspects of their sexual interaction with the estrous female; rather, they appeared specifically unable to perform the reflexive pelvic thrust pattern normally associated with mounting. We here report, however, that the ability to perform mounts with pelvic thrusts was temporarily restored in the vast majority of MPOA-injured males by the i.p. administration of the ergot derivative, lisuride. About 50% of these MPOA-damaged males even ejaculated, often after a low number of intromissions and short ejaculation latencies. On the other hand, injections of naloxone (an opiate receptor antagonist) failed to activate mounting in MPOA-lesioned or castrated rats. On the basis of these findings the possible ways in which steroid hormone-sensitive brain areas might interact with monoamine-containing pathways are discussed.U