The effects of ATP and other nucleotides on the cytosolic Ca2+ concentration ([Ca2+]i) of single immunocytochemically typed anterior pituitary (AP) cells have been studied. ATP increased [Ca2+]i in a large percentage (60-88%) of all five AP cell types: lactotropes, somatotropes, corticotropes, gonadotropes, and thyrotropes. Additivity experiments suggest the presence of at least two different receptors, one accepting both ATP and UTP (U receptor), producing Ca2+ release from the intracellular stores, and the other preferring ATP (A receptor), producing Ca2+ (and Mn2+) entry. The characteristics of the U and A receptors were consistent with those of P2Y2 and P2X2, respectively, and their distribution in the different AP cell types was not homogeneous. The presence of other ATP receptors such P2Y1 or P2X2/P2X3 heteropolymers in a small fraction of the cells cannot be excluded. Thus functional ionophoric P2X receptors, which are typical of neural tissue, are also present in the pituitary gland and could contribute to regulation of the gland's function.