A fine structural study has been made of the vesiculated nerve profiles of the submucous plexus of both normally innervated and extrinsically denervated segments of guinea-pig ileum. Two types of nerve profiles could be readily distinguished by their vesicular content after conventional fixation. The first type, comprising 5% of all intrinsic profiles, consisted of predominantly small vesicles containing electron dense material which usually formed a ring around the inner face of the vesicular membrane but sometimes partially or completely filled the vesicle. These profiles, termed ring-vesicle-containing profiles, remained after extrinsic denervation and their vesicular content did not change following injection of reserpine or 5-hydroxydopamine. Thus ring-vesicle-containing profiles are not noradrenergic. Profiles which were positive for the uranaffin method were similar in morphology and frequency of occurrence to ring-vesicle-containing profiles, although it is not possible to say that they are the same. The second type of profile, comprising 95% of all intrinsic profiles, contained varying proportions of large granular and small clear vesicles. These heterogeneous profiles were present in both normally innervated and extrinsically denervated tissue. Their vesicular content did not change following injection of reserpine, however, some profiles of this type in normally innervated, but not in extrinsically denervated, intestine contained electron dense deposits after injection of 5-hydroxydopamine. This means that noradrenergic profiles are a subpopulation of the heterogeneous profiles in normally innervated tissue. Analysis of intrinsic heterogeneous profiles showed that the proportion and packing density of large granular vesicles formed continuous distributions which did not provide any basis for further subdivision of this type of profile. Ring-vesicle-containing and heterogeneous profiles often formed synapses with neuronal cell bodies and processes. Two rarer types of profiles were also seen. The first type contained mainly small flattened vesicles which took up 5-hydroxydopamine and was not present in extrinsically denervated tissue. This type, like the group described above, is considered to be noradrenergic. The second rare type contained large numbers of lysosome-like dense bodies and vesicles of different sizes and content and was seen in both normally innervated and denervated tissue. This type probably represents spontaneously degenerating nerve profiles.