E-cadherin is an intercellular adhesion protein expressed by most epithelia. Decreased expression of E-cadherin correlates with tumor aggressiveness in most carcinomas. In renal cell carcinoma (RCC), however, this correlation is not well established and the prevalence of negative tumors is higher than in other carcinomas. Our immunofluorescence study of alpha-catenin expression in 20 RCC cell lines revealed a typical honeycomb staining pattern in all of the lines, whereas only six expressed E-cadherin. This suggested that other cadherins are expressed in RCC lines. Indeed, immunoprecipitation with an anti-alpha-catenin antibody resulted in coprecipitation of proteins of Mr 125,000-135,000. Using Western blot, these proteins react with a pan-cadherin antibody. To identify these cadherin related proteins, RT-PCR using degenerated primers and sequence comparisons was carried out. We then assessed the expression of the identified cadherins. N-cadherin mRNA was present in all cell lines; and cadherin 6 mRNA was seen in 16 lines. Cadherin 11 (mRNA) and E-cadherin (protein) were expressed in five and six lines, respectively. A cadherin 4 transcript was observed in only one line, whereas no P-cadherin protein could be detected. Expression of the four main cadherins was also found in normal kidney (two samples tested) and RCC specimens (four samples). Thus, RCC and normal kidney express a complex set of cadherins.