Secretion of gonadotropic hormones from pituitary gonadotropes in response to gonadotropin-releasing hormone (GnRH) is essential for regulation of reproductive potential. Gonadotropes from male rats exhibited an unusual form of cellular excitation that resulted from periodic membrane hyperpolarization. GnRH induced an oscillatory release of intracellular Ca2+ via a guanosine triphosphate (GTP) binding protein-coupled phosphoinositide pathway and hyperpolarized the gonadotrope periodically by opening apamin-sensitive Ca(2+)-activated K+ (SK) channels. Each hyperpolarization was terminated by firing of a few action potentials that may result from removal of inactivation from voltage-gated Na+ and Ca2+ channels.