Noradrenergic nerves in human jejunum and distal ileum were identified at the light microscopic level by fluorescence histochemistry and at the ultrastructural level by 5-hydroxydopamine loading in vitro and by the chromaffin reaction. The myenteric and submucous ganglia contained dense arrays of varicose noradrenergic fibers; the muscularis externa, muscularis mucosae, intestinal glands, and villi were sparsely supplied. Enteric axon profiles that had taken up 5-hydroxydopamine contained variable proportions of flattened, small round, and pleomorphic large vesicles all containing electron-dense material. Chromaffin-reactive enteric axon profiles and some enteric profiles in conventionally fixed untreated intestine contained similarly shaped vesicles. After 5-hydroxydopamine loading, noradrenergic nerves supplying blood vessels contained large round and small round vesicles with dense cores. Noradrenergic varicosities were concentrated near the edges of myenteric ganglia and were randomly distributed in submucous ganglia. Noradrenergic axons occasionally formed synapses on nerve processes in both myenteric and submucous ganglia, and on rare occasions, on nerve cell bodies in myenteric ganglia. Nonnoradrenergic axon profiles containing small round vesicles with granular inclusions (ring vesicles) were also found in human small intestine. The distribution and ultrastructure of noradrenergic nerves in human small intestine is similar to that in other mammals except for the occurrence of synapses in human ganglia.