Galanin is widely distributed throughout the rat neural and endocrine system with the highest concentration in the anterior pituitary. The effects of galanin were investigated in rat tumor pituitary cells (GH3/B6). A single stimulation with galanin caused prolactin (PRL) and growth hormone (GH) release within a narrow range of concentrations (10(-11)-10(-9)M). However, secretory responses were not consistently observed upon subsequent galanin stimulation. Galanin triggered a rise in cytosolic Ca2+ (burst in [Ca2+](i) transients) with a similar responsiveness. By contrast, no change in PRL mRNA was detectable in response to the peptide. These data suggest that galanin which binds to high-affinity receptors in anterior pituitary cells can exert subtle modulations of pituitary cell functions.