The secretion of alpha-melanophore-stimulating hormone (alpha-MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuropeptides. The majority of these cells (80%) display spontaneous Ca2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca2+ ([Ca2+]i) in the melanotrope cell, we have examined the action of well known alpha-MSH secretagogues on the Ca2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine (gamma-aminobutyric acid, GABAA agonist), baclofen (GABAB agonist) and neuropeptide Y evoked a rapid quenching of the spontaneous Ca2+ oscillations, whereas the secreto-stimulant sauvagine, an amphibian peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.