TP-40 is a hybrid fusion protein produced by recombinant technology and consists of a molecule of transforming growth factor-alpha (TGF-alpha) fused to the Pseudomonas exotoxin PE-40. A panel of human and murine bladder cancer cell lines was found to be universally sensitive in vitro to TP-40 in a clonogenic assay. All lines expressed receptor for epidermal growth factor (EGF), though none demonstrated gene amplification for the EGF receptor. The sensitivity to TP-40 may be blocked by preexposure to EGF. Six human bladder tumors taken directly from patients were all sensitive in vitro to TP-40; these included well-differentiated tumors. TP-40 may prove to be effective as an intravesical agent in bladder cancer via selective targeting to cells that express EGF receptors, as do the majority of human bladder cancers.