Cells of the pituitary tumour cell line GH(4) C(1) were exposed to epidermal growth factor, estradiol and insulin for 5 days, a treatment which resulted in 1) increased prolactin storage in secretory granules, 2) the loss of spontaneous [Ca(2+) ](1) oscillations, and 3) a selective reduction of the protein G(s) α, seen in immunoblots, cholera toxin labelling, and vasoactive intestinal peptide stimulation of adenylyl cyclase. In contrast, the glucocorticoid dexamethasone, which increases the expression of G(s) α, partially restored spontaneous [Ca(2+) ](1) oscillations and decreased prolactin storage. It is concluded that G(s) α levels in tumoral cells result in spontaneous electrical activity which may empty prolactin stores by the continuous activation of exocytosis.