The reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the axon terminals presynaptic to the submucous neurons of guinea-pig intestine following unilateral cervical vagotomy was studied by electron microscopy. The reaction product of diaphorase was localized only in the axon terminals that contained predominantly small agranular vesicles, and it was usually deposited around the vesicles. The terminals that contained predominantly large granular or flattened vesicles did not display any signs of diaphorase reactivity. Although there were only few diaphorase-positive submucous neurons in the small intestine, a considerable number of diaphorase-positive axon terminals was observed in the submucous ganglia of the small intestine in the control animals. Ten days after vagotomy, the quantitative study showed that when compared with the control animals, the number of diaphorase-positive terminals in the submucous ganglia of duodenum, mid-small intestine and colon in the vagotomized animals was reduced (P < 0.05). When the NADPH-d-positive terminals were examined in closer detail, it was found that only a small proportion of them showed signs of degeneration as evidenced by the swelling and vacuolation of their contents of mitochondria, with disrupted cristae and clumping of synaptic vesicles. It was therefore concluded that at least some of the diaphorase-positive axon terminals in the submucous ganglia of guinea-pig intestine originated from the vagus nerve.