To determine the histological structure and autonomic innervation of the vesico-ureteric junction (VUJ) in cases of primary ureteric reflux, to compare the results with those reported previously for non-refluxing VUJs and thus determine possible structural anomalies which could be responsible for vesico-ureteric reflux (VUR). Nineteen specimens of VUJs with reflux were obtained from four males and 10 females undergoing ureteric reimplantation. Serial frozen sections were cut and stained either with Masson's trichrome or immunostained for protein gene product (PGP 9.5), a general nerve marker, dopamine beta hydroxylase (D beta H), a marker for noradrenergic nerves, or neuropeptide Y (NPY). Longitudinally orientated muscle bundles of narrow diameter accompanied the ureter to its termination at the ureteric orifice. Where they merged with those of the superficial trigone. In some specimens, an additional muscle component was identified, situated on the outer aspect of the ureteric muscle coat, consisting of an incomplete layer of distinctive muscle whose constituent cells formed an interlacing mesh-work. Occasionally, specimens included detrusor muscle which consisted of relatively large diameter compact bundles separated from the ureter by a connective tissue sheath. D beta H- and NPY-immunoreactive (-IR) nerves were numerous among the ureteric muscle bundles. Many NPY-IR nerves occurred within the detrusor muscle while D beta H-IR nerves were mainly perivascular. When present, the outer muscle component was richly innervated by both D beta H- and NPY-IR nerves. PGP immunoreactivity varied among regions in the same section, PGP-IR nerves frequently being less numerous than those containing D beta H or NPY. These results indicate that the morphology of the VUJ in cases of VUR is indistinguishable from the normal VUJ described previously. Furthermore, the density and distribution of D beta H- and NPY-IR nerves is identical to that in controls. However, the antigenicity of PGP in the reflux specimens appears to be masked in some regions by an unknown factor.