Serotonin decreases oxygen consumption by hypothalamic, but not by cortical homogenates incubated with glucose in a Warburg apparatus. This decrease is not sex related, since it is observed in hypothalamic homogenates from castrated as well as from intact rats. As castration increases oxygen consumption, the inhibition is greater in the castrated than in the intact group. When pyruvate is used as substrate, the inhibitory action of serotonin is observed, not only in homogenized hypothalamus from castrated rats, but also from intact and castrated animals injected with gonadal steroids or adrenalectomized. Neither citrate nor succinate oxidation is inhibited by serotonin in normal or castrated rats. Oxygen consumption of the male hypothalami is always higher than that of the female and this difference is maintained even when substrates and/or serotonin are added. As the difference is not modified by castration and is observed regardless of the substrate used, it is suggested that such variation may be related to the process of sexual differentiation of the nervous system.