This experiment was undertaken to elucidate the concept that alterations of sex hormone and oxytocin in the systemic circulation exert remarkable influences upon the excitabilities of the multisynaptic pathways in the central nervous system. Observations were made on ovariectomized matured cats and rabbits with or without estrogen or progesterone treatment. The electrodes were permanently implanted into the brain and around the sciatic nerve and the dorsal root of the sacral segment, recording the evoked potentials in the hypothalamus, mesencephalic reticular formation (RF) and the medial lemniscus (ML) by electrical stimulation of the contralateral sciatic nerve, the dorsal root of the sacral segment, or by electrical stimulation of the hippocampus and amygdala. The results were as follows:<BR>1. During estrus induced by estrogen-progesterone priming of ovariectomized animals, the evoked potentials in the periventricular arcuate nucleus (ARC) and the RF to which single shock stimuli were delivered from the sciatic nerve were facilitated as compared with those during anestrus, while those in the same regions by stimulation of the dorsal root of the sacral segment were inhibited. In the non-estrogen primed, ovariectomized animals, a subcutaneous in jection of progesterone (5mg) evoked the opposite response in the ARC and the RF from that during estrus. Sacral stimulation increased the potential while stimulation of the sciatic nerve inhibited the potential.<BR>The hippocampally evoked potential in the ARC was inhibited in estrus, while facilitated after subcutaneous injection of progesterone (5mg). On the contrary, the amygdalarly evoked potential was facilitated during estrus, and inhibited after a subcutaneous injection of progesterone (5mg). On the basis of observations of the evoked potential and EEG pattern it was suggested that LH (0.3U.) had a facilitatory effect on the activity of the hippocampushypothalamus system and an inhibitory effect on that of the amygdala-hypothalamus system. The effect of FSH (100 I.U.) on these two systems was the complete reverse of the LH effect. Furthermore, it was noted that the RF responded to FSH independent of the hypothalamic response.<BR>2. The sacrally evoked potential in the ARC was facilitated after an intravenous in jection of oxytocin (0.3-0.4 I.U.) during estrus, and this was inhibited during the period of highly concentrated progesterone in the blood; the sciatically evoked potential in this region was inhibited after oxytocin administration at estrus, and facilitated after subcutaneous injection of progesterone (5mg).<BR>Many more facilitatory and inhibitory effects upon the evoked potential were observed in the RF than in the ML at the midbrain level by the peripheral afferent volley after intravenous injection of oxytocin, as well as during the period of anestrus and estrus.<BR>The facilitatory or inhibitory effect of the evoked potential in the ARC elicited by the afferent volley was noticeably depressed after lesion of the RF, while a lesion of the ML exerted only a slightly depressing effect upon the evoked potential recorded in the same area of the ARC.<BR>In short, it was observed that during estrogen dominance over progesterone, for example at estrus, the function of the RF was to facilitate transmission of somato-sensory afferent impulses to the higher center, and the inhibit viscerosensory afferent impulses. Conversely, if the influence of progesterone exceeded that of estrogen, for example during pregnancy, the activity of the RF was reversed; transmission of the peripheral somato-sensory afferent impulses to the higher center was inhibited while transmission of viscero-sensory afferent impulses was facilitated. When oxytocin increased in systemic circulation the evoked potentials are inverted in both circumstances.