In an attempt to study the inhibitory effects of serotonin on spontaneous ovulation, the monoamine was administered subcutaneously to rats with 4-day oestrous cycles. Administration (50 mg/kg) at 5.00 p. m. on the day before pro-oestrus interfered with ovulation without affecting vaginal cornification, uterine ballooning or mating. This effect on ovulation could be overcome with methysergide, a specific antagonist of serotonin. Administration, at appropriate times, of LH or oestradiol benzoate or the stimulus provided by mating prevented the inhibitory effects of serotonin. implicating a central rather than a peripheral mechanism in interference with ovulation. This was further confirmed by the persistence in the serotonin-treated animals of high levels of pituitary LH, comparable to pro-oestrous levels. It is probable that serotonin blocked ovulation by augmenting the inhibitory effects of serotoninergic fibres in the hypothalamus. It is postulated on the basis of the present results and those reported in the literature that the hypothalamus exercises a dual control over ovulation, inhibitory influences being transmitted through serotonin-linked neurones while stimulatory effects are delivered via catecholaminergic fibres to neurones which synthesize releasing factor(s) for the ovulating hormone. It is postulated that a certain degree of balance in favour of the catecholaminergic system is necessary for the occurrence of ovulation. Inhibition of ovulation occurs whenever the serotoninergic system gains dominance over catecholaminergic system. The theory can account for the effects on ovulation of a multitude of chemically diverse agents reported in the literature.