Two cell lines, SKR1 and NKK1, were established from renal cell carcinomas (RCC) with different histopathologic characteristics: SKR1 from grade 3, solid type, pleomorphic cell type carcinoma in a 66-year-old male and NKK1 from grade 2, alveolar type, clear cell carcinoma in a 49-year-old female. Electron microscopic study showed the presence of microvilli on cell surface and desmosome-like structures between cells in both lines. Doubling time and plating efficiency of SKR1 were 28 h and 37%, respectively, whereas those of NKK1 were 45 h and 22%, respectively. The chromosome number of both cell lines was 100% aneuploid with a mode of 74 chromosomes for SKR1 and 84 for NKK1. Both SKR1 and NKK1 induced tumors at the site of subcutaneous injection of nude mice. The morphologic characteristics of the tumor were similar to those of each original tumor. NKK1 was about 20 times more resistant to doxorubicin and vinblastine as compared to SKR1. Expression of P-glycoprotein was considered to be one of the factors responsible for such multidrug resistant phenotype of NKK1 cells. These two lines with different chemosensitivity may be a useful model for developing new therapeutic strategies for RCC.