Polyclonal antibodies to the brush border membrane of the human renal proximal tubule were found to identify two proteins with apparent molecular weights of 35,000 and 46,000 daltons. The antigens are distinct in their molecular weights from other antigens that have been localized to the human proximal tubular brush border. The antibodies were extensively studied for their immunoreactivity to fixed, embedded tissue sections by indirect immunoperoxidase staining. These sections were from 36 primary and 37 metastatic renal cell carcinomas, three renal oncocytomas, 87 cases of 28 different types of neoplasms, and 33 different types of normal tissues. Ninety-four percent of primary and 78% of metastatic renal cell carcinomas demonstrated expression of the antigens. Eight cases in which both primary tumor and its metastases were available revealed a general quantitative decrease in expression of the antigens in the metastases. Specificity analysis revealed immunoreactivity to the luminal surfaces of cells lining the epididymis, breast lobule, and bile ductules; the cytoplasm of the submandibular gland ductules; and to some adenocarcinomas of lung, breast, and small intestine, astrocytomas of brain, and squamous carcinomas of skin. The antibodies may be of some utility in the surgical pathology laboratory to help determine the primary site of metastatic clear cell tumors and may also be of use in the in vitro differentiation of renal epithelial cells. Development of monoclonal antibodies to these antigens may improve specificity and clinical utility.