Guanosine 3',5'-cyclic monophosphate (cGMP) is a second messenger generated in response to hormones or neurotransmitters in various tissues and cells. In parotid acinar cells, the activation of muscarinic cholinergic and beta-adrenergic receptors induces an increase in intracellular cGMP. However, the mechanism of cGMP production in parotid acinar cells has not been well elucidated. cGMP production is induced by the activation of guanylyl cyclases, which are directly activated by nitric oxide (NO). NO plays an important role as an inter- and intracellular signal molecule in various organs and cells. Biosynthesis of NO is catalyzed by NO synthase (NOS), and NO generation is controlled by the regulation of NOS activity, for example by Ca2+. We have studied the regulation of NOS activity, NO generation and cGMP production in rabbit parotid acinar cells, and have demonstrated a functional Ca2+-NO-cGMP signaling pathway.