In order to further investigate the involvement of FGF1 and FGF2 in the transitional cell carcinoma of the bladder (TCC), we compared the expression of FGF1, FGF2 and their membrane binding sites by biochemical and immunological methods in both human normal urothelium and transitional cell carcinoma of the bladder. Using a specific enzyme immunoassay (EIA), we observed that neoplastic tissue exhibited a lower FGF2 content than normal tissue. FGF1 and FGF2 Western-blot analysis revealed in both types of tissues a major FGF1 form with a low molecular weight (14 kDa) and a single FGF2 form (21 kDa). Immunohistological studies showed that FGF1 was specifically located in normal or transformed urothelial cells, while FGF2 was associated with bladder stroma. Binding analysis in tissue membrane preparations revealed a dramatic drop in both high and low affinity binding sites for FGF2 in TCC bladder in comparison to normal bladder. FGF2 cross-linking experiments illustrated a qualitative modification of FGF2 binding complexes in tumors. These data suggest that invasive bladder carcinoma is associated with modifications of FGF1 and FGF2 tissue levels and alterations in the characteristics of the FGF2 membrane binding sites.