A possible inter-relationship between oestrogen, α-melanotrophin (αMSH) and NA in the ventromedial nucleus (VMN) has been studied in ovariectomised-adrenalectomised rats primed with a low dose of oestradiol benzoate (2 or 5 µg OB), which induces receptivity in approximately half the rats. Priming with OB increased NA turnover in the VMN (as assessed by the decline in NA concentration 1 h after 250 mg/kg α-methyl tyrosine αMT) and also enhanced the release of NA from basal medial hypothalamic fragments in vitro. This occurred whether the rats were receptive or non-receptive. Injection of 20 µg/ rat αMSH, 4 h before autopsy in OB-primed rats, reduced NA turnover in the VMN but only in the receptive animals. αMSH had no effect on NA content in the VMN, but prevented the decline normally induced by the αMT, indicating an inhibition of release. Application of 1 µg/ml αMSH to incubated hypothalamic fragments enhanced release of NA in the tissue obtained from untreated controls and the OB-non-receptive group, but had no effect on the tissue of the OB-receptive animals. Perhaps NA release had already occurred in vivo in the latter group. αMSH (100 ng/side/rat) and NA (20, 200 and 2,000 ng/side/rat) were injected into the VMN of ovariectomised-adrenalectomised rats primed with 1 µg OB. Both agents stimulated lordosis in non-receptive animals with a peak activity at 60 min. The effect of αMSH declined over the next 2 h, but the maximum effect of 200 and 2,000 ng NA was maintained until the end of the test at 4 h. Neither agent affected behaviour in receptive animals. Intra-VMN administration of the β-adrenergic antagonists, propranolol and metoprolol (both at 400 ng/side/rat) reduced the effect of αMSH and the former also antagonised the effect of NA, while the α-adrenergic antagonist, phentolamine (200 µg), was ineffective. These results show that αMSH and NA in the VMN stimulate female sexual behaviour and the effect of αMSH may be mediated by NA acting on β-receptors. αMSH may act by enhancing the release of NA, but once receptivity is initiated, αMSH appears instead to reduce NA release and thus to terminate the period of receptivity.