In the present study we have examined ten cases of the chromophobe type renal cell carcinoma. This type of tumor is distinguished from the other carcinomas of the kidney with light cytoplasm (formerly called "hypernephroid") by (a) a positive Hale's iron colloid stain of the cytoplasm, (b) the occurrence of numerous invaginated vesicles within the cytoplasm that resemble the invaginated vesicles of intercalated cells of the collecting duct system, and (c) a positive immunoreaction of both the plasma membrane and the cytoplasm with antibodies to the epithelial membrane antigen (EMA) and carbonic anhydrase C (CAC), respectively. Unlike oncocytomas, which also express CAC and EMA, the chromophobe renal cell carcinoma does not express the erythrocyte anion exchanger band 3. These findings strongly indicate that chromophobe renal cell carcinomas as well as oncocytomas of the kidney are histogenetically related to the two populations of intercalated cells of the collecting duct system. Thus, both tumors represent examples of renal tumors which disprove the broadly accepted hypothesis that all epithelial tumors of the kidney are histogenetically related to the proximal tubule.