Tumor-suppressor genes can be transferred into tumor cells in vivo using a replication-defective adenoviral vector. P53 mutations are frequent in bladder cancer, and adenovirus-mediated p53 gene transfer is growth-inhibitory to bladder cancer cells in vitro. The vector Ad5CMV-P53, which contains human wild-type p53, is being administered intravesically to patients with bladder cancer in a phase I clinical trial. The results of this study will provide the basis for phase II and phase III trials in which gene therapy will be integrated with existing therapies for improved local control and opportunities for bladder preservation.