We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract, 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%) of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle invasion and the remaining was G1, pTa tumor with subsequent recurrence of multiple tumors. The other 2 cases (6.3%) with invasive transitional cell carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross rearrangement of EGFR gene was detected in transitional cell carcinoma. On the other hand, renal cell carcinomas and prostatic carcinomas had neither amplification nor gross rearrangement of these 3 genes. These results suggest that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have a specific role in carcinogenesis and in progression of transitional cell carcinoma through their gene amplifications.