The effect of 5-hydroxytryptophan (5-HTP), a serotonin precursor, and p-chloroamphetamine (PCA), a serotonin neurotoxin, selective for serotoninergic neurons, that depletes serotonin (5-HT) levels in brain, on the luteinizing hormone (LH) release response to estrogen-progesterone (E-P) was studied in prepubertal female rats of different ages. E-P decreased LH levels on days 16, 18 and 20, increasing the levels of the pituitary hormone at day 26 of age. Destruction of the serotoninergic system advanced the onset of the positive feed-back mechanism, since the rats pretreated with PCA showed at day 20 an LH release by E-P administration while in the controls of the same age the ovarian hormones decreased the LH concentration. On the other hand, PCA potentiated the positive feed-back mechanism of E-P on LH in 26-day-old rats, while at this age the LH release response to E-P was significantly reduced by the administration of 5-HTP. These results suggest that the serotoninergic system has an inhibitory effect on the development of the positive feed-back of ovarian steroids on LH secretion, that could be representative of a regulatory participation of serotonin in the onset of puberty. 5-HTP stimulated LH release on days 16, 18 and 20, but did not modify the LH concentration of day 26. Since between 20 and 26 days of age the positive feed-back mechanism matures, the possibility arise that the modification in the effect of serotonin on LH release on day 26 is connected with the physiological changes in the gonadotropin control that occur after day 20 in the female rat.