The role of serotonin (5-HT) in generating the spontaneous preovulatory surge of luteinizing hormone (LH) has been investigated by studying the effect of ketanserin (a mixed 5-HT2/alpha(1) adrenoreceptor antagonist); the selective 5-HT2 receptor antagonist, ritanserin; and the selective cr, adrenoreceptor antagonist, prazosin, on the plasma concentrations of LH during the afternoon of proestrus in conscious Wistar rats. Sequential blood samples for hormone estimation were taken through intra-atrial cannulae previously implanted under halothane anesthesia. All three drugs blocked the LH surge; ketanserin, but not ritanserin or prazosin, also blocked basal LH release. These results provide the first robust evidence for the fact that a 5-HT2 receptor as well as an ct, adrenoreceptor mechanism is involved in the LH surge generator.