To clarify the role of basic fibroblast growth factor (FGF-2) in the drug resistance of bladder cancer, we transfected the FGF-2 gene into HT1376, an FGF-2 negative human bladder cancer cell line. The FGF-2-transfected cell lines exhibited three- to four-fold higher resistant potential to cisplatin than the vector-only transfected control cell lines in vitro. When cisplatin was injected intraperitoneally after s.c. implantation of HT1376 sublines into nude mice, FGF-2 transfectants formed tumors about twice as large as did controls. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among these cell lines without cisplatin treatment. Furthermore, DNA degradation following cisplatin treatment was markedly suppressed in FGF-2 transfectants compared to control cells. These results suggest that the expression of the FGF-2 gene plays an important role in the acquisition of the cisplatin-resistant phenotype of bladder cancer, probably through the protection against cisplatin-induced apoptosis.