Secretory activity of the anterior pituitary gland is regulated by the brain through stimulatory and inhibitory substances released from nerve endings in the median eminence of the hypothalamus and carried by the adenohypophysial portal blood system to their respective target cells. These hypothalamic influences are modulated by the feedback action of peripheral hormones. Prolactin (PRL) secreting cells are, at least partially, under the stimulatory influence of thyrotropin releasing hromone (TRH) and of oestrogens. However, they are mainly controlled by inhibitory substances among which dopamine (DA) is one of the most potent in vivo as well as in vitro. The inhibitory effect of DA is reversed by oestrogen in vitro. The mechanism by which these factors interact on their target cells is poorly understood. The recent discovery that anterior pituitary cells are excitable and that they are able to generate Ca2+-dependent action potentials has led to the suggestion that these effects are involved in a stimulus-secretion coupling at the membrane level. In this paper, we report that DA inhibits both the spontaneous and TRH-induced action potentials in clonal PRL pituitary cells. In addition, oestradiol-17 beta is able to reverse the inhibitory effect of DA.