This study examined the distribution of NADPH-diaphorase (NADPH-d) activity in cat pancreatic ganglia and the electrophysiological effects of nitric oxide (NO) donors, NO and the effect of endogenously released NO. The majority (64%) of pancreatic ganglion neurons stained positive for NADPH-d. Large nerve trunks contained numerous non-varicose NADPH-d positive fibers. NADPH-d positive nerve fibers within individual ganglia were varicosed. L-Arginine, sodium nitroprusside and NO, applied in the vicinity of the impaled neuron, evoked a hyperpolarizing response and initiated fast excitatory postsynaptic potentials (EPSPs) in the majority of neurons tested. The hyperpolarizing response was not affected by low Ca2+ (0.1 mM), high Mg2+ (15 mM). Pretreatment with nitro-L-arginine increased the amplitude of slow EPSPs in about 50% of neurons tested. These results support the hypothesis that NO plays a role in ganglionic transmission in the cat pancreas.