The dorsal region of the anterior frontal lobe neocortex has an inhibitory function in the secretion of luteinizing hormone (LH) and ovulation. It is suggested that the anterior frontal lobe neocortex regulates the secretion of LH through the nerve circuit composed of the anterior median limbic area, the thalamic dorsomedial nucleus and the basolateral amygdaloid nucleus which are innervated by serotonergic neurons. In the present study, the relationship between the inhibitory effect of the frontal lobe neocortex on LH secretion and serotonergic neurons from the brain stem raphe nuclei was studied in 4-day vaginal cycle female Wistar rats. Electrochemical stimulation (DC 120 microA, 30 sec.) of the anterior frontal lobe neocortex just before the critical period of ovulation on the day of proestrus blocked the preovulatory surge of LH and ovulation. Electrochemical stimulation of the anterior frontal lobe neocortex just before the critical period but 120 min. after administration of rho-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) could not block the preovulatory surge of LH and ovulation. Electrochemical stimulation of the anterior frontal lobe neocortex just before the critical period but 120 min. after excision of the median raphe nucleus blocked the preovulatory surge of LH and ovulation. Electrochemical stimulation of the anterior frontal lobe neocortex just before the critical period but 120 min. after excision of the dorsal raphe nucleus could not block the preovulatory surge of LH and ovulation. These results suggest that serotonergic neurons ascending from the dorsal raphe nucleus are involved in the inhibition of LH secretion and ovulation caused by electrochemical stimulation of the anterior frontal lobe neocortex and that the secretion of serotonin is necessary for the inhibition of LH secretion.