The c-erb B-2/neu gene encodes a cell-surface glycoprotein with extensive homology to, but distinct from, the epidermal growth-factor receptor. In this study, we compared the c-erb B-2/neu gene amplification and expression of tissue specimens obtained from the bladders of normal controls and patients with high-grade transitional cell bladder carcinoma. Southern blot analysis of DNAs from 24 patients and 5 controls showed 2 cases of c-erb B-2/neu gene amplification in patients and none in controls. Western blot analysis demonstrated that c-erb B-2/neu was expressed in 67.6% (23/34) of patient specimens but in none of the controls (0/5). This finding agreed with the result of immunohistochemical staining, which showed that tissue from 74.3% (26/35) of the patients and none of the controls (0/7) showed positive immunofluorescence staining. This is the first report suggesting that c-erb B-2/neu gene amplification may be associated with human bladder carcinogenesis.