The structure of the nerve fibres in the chronically isolated cat ileum was studied by fluorescence and electron microscopy after 5,6-dihydroxytryptamine (5,6-DHT) treatment. Residual fluorescence rapidly disappears after administration of 5,6-DHT. Under the electron microscope, degeneration of most of the nerve processes containing a special population of 120-to 140-nm diameter granular vesicles could be observed. Also the degeneration of presynaptic terminals in the local ganglia was observed frequently. Some degenerating nerve fibres were found in the inner muscular layer, in the connective tissue surrounding Lieberkühn’s glands, and in the stroma of the villi. The axons (and/or other nerve processes) undergoing degeneration are assumed to belong to the serotoninergic neurons of the local ganglia. A substantial number of nerve cell processes remaining intact after 5,6-DHT treatment contain different population of vesicles: either 30- to 60-nm agranular and 100- to 120-nm granular vesicles or 30- to 60-nm agranular and 160- to 200-nm diameter neurosecretory type vesicl