The interaction of stimulatory and inhibitory receptors at the level of adenylate cyclase has been studied in three systems. In rat anterior pituitary, vasoactive intestinal peptide (VIP) stimulates adenylate cyclase and prolactin release in the mammotrophs. Dopamine can block both of these responses through action at a D-2 receptor. The rat pituitary GH3 cell line provides a single population of cells which also respond to VIP with both adenylate cyclase activation and prolactin secretion. Muscarinic agonists can inhibit both basal and VIP-stimulated adenylate cyclase, as well as prolactin secretion, in this cell line. Muscarinic receptors in rat striatum also inhibit adenylate cyclase and concurrently stimulate a high affinity GTPase, suggesting that inhibitory receptors may affect adenylate cyclase via action on a GTPase. The GH3 cells will allow us to examine this question further in a pure cell population.