The effect of stimulation of the frontal lobe cortex on the release of luteinizing hormone (LH) and ovulation was studied in female rats. Electrochemical stimulation (anodic DC) was applied through monopolar stainless-steel electrodes chronically implanted in the non-anesthetized freely-behaving animals bearing a plastic cannula inserted into the jugular vein for blood sampling. In rats, on the day of proestrus, stimulation (100 uA/30 sec) of the medial cortical surface in the superficial and deep layers of the medial precentral area and of the anterior cingulate area blocked ovulation in about 80% of the animals. A similar effect was seen when the stimulus was applied in the deep layers of the prelimbic and infralimbic areas. On the contrary, stimulation in the superficial layers of these latter two areas, as well as in the superficial and deep layers of the retrosplenial cortex, did not affect normal ovulation. The preovulatory discharge of LH was blocked in the animals which failed to ovulate. The degree of inhibition exerted by the anterior cingulate area and the prelimbic area on ovulation and LH surge was proportional to the amount of current applied. Stimulation of the anterior cingulate area also blocked the release of LH induced by the injection of progesterone into ovariectomized estrogen-primed rats. Furthermore, electrochemical stimulation of the anterior cingulate area inhibited the rise of LH in the serum induced by electrical stimulation of the medial preoptic area of ovariectomized estrogen-injected rats, but it failed to affect that resulting from electrical stimulation of the medial basal hypothalamus. On the other hand, stimulation of the lateral cortical surface and the ventral cortex of the frontal lobe on the day of proestrus affected normal ovulation and LH surge only when the stimulus was applied in the agranular insular area which also exhibited an inhibitory action. It is concluded that certain areas of the frontal lobe cortex related to limbic structures exert an inhibitory influence on ovulation and LH secretion.