The present study aims to investigate the effect of nitric oxide (NO) on histamine-stimulated acid secretion of gastric glands. An NO donor, sodium nitroprusside (SNP), and inhibitors of NO synthase such as N-G-nitro-L-arginine methyl ester (LNAME) and N-G-nitro-L-arginine (L-NNA) with or without L-arginine, a substrate for NO synthase, were added to isolated rabbit gastric glands with the secretagogues. Acid secretion, intracellular concentrations of cGMP and cAMP and lactic dehydrogenase (LDH) release were determined. L-NAME and L-NNA increased stimulated acid secretion, which was reversed by L-arginine. SNP inhibited stimulated acid secretion concentration-dependently; the inhibition was accompanied by an increase in the intracellular cGMP, but neither related to cAMP nor LDH release. In conclusion, NO produced in large quantity by an NO donor inhibits histamine-stimulated acid secretion of isolated rabbit gastric glands.