The role of ras oncogenes in the pathogenesis of renal cell carcinoma is unclear. We have previously shown that insertion of a mutated ras oncogene into cultured human proximal tubular cells, the normal counterpart of renal cell carcinomas, initiates a series of transformation events which results in cells possessing a renal cancer phenotype. These data suggested a role for mutated ras genes in the initiation and maintenance of this disease. Therefore, to assess the involvement of ras genes in renal carcinogenesis, 51 primary and metastatic renal carcinomas, including three oncocytomas, were analyzed for point mutations in codons 12, 13 and 61 of the Ha-ras, Ki-ras and N-ras proto-oncogenes using polymerase-catalyzed chain reaction methodology. A mutated Ha-ras gene was found in one renal cancer metastatic to lung for an overall incidence of 2%. These data indicate that ras oncogenes, activated by point mutations, do not play a major role in the initiation, maintenance or metastases of renal carcinomas.