1. We have previously shown that [¹²⁵I]‐endothelin (ET) receptor binding is localized almost exclusively to the fenestrated endothelial cells of glomerular capillaries and peritubular capillaries in the rat kidney following systemic administration of the radioligand in vivo. Because of the lack of specific ET receptor binding in other glomerular and tubular structures following in vivo labelling, we undertook further studies, using electron microscopic autoradiography and ET receptor subtype selective ligands, to investigate whether other renal components also contain ET receptor binding and, if so, to determine the cellular localization of the ET receptor subtypes, ET_A and ET_B, following in vitro labelling.

2. At the electron microscopic level, ET binding sites were localized primarily to the fenestrated endothelium of glomerular and peritubular capillaries of the cortex, inner stripe of the outer medulla and the inner medulla. ET binding sites also occurred overlying renomedullary interstitial cells (RMIC) of the inner medulla.

3. The ET_B receptor selective agonist, sarafotoxin 6c (S6c), abolished ET binding in the vascular endothelium throughout the kidney, while the ET_A receptor selective antagonist, BQ123, was without effect. Both BQ123 and S6c partially inhibited the binding in the RMIC of the inner medulla.

4. These results indicate that ET receptor binding in the fenestrated endothelium in the glomerular capillaries and peritubular capillaries belongs mainly to the ET_B subtype, whereas both ET_A and ET_B subtypes are present in the RMIC.