Major progress has been made in the treatment of patients with advanced urothelial tract tumors, using a systematic phase II approach in selected patients. At this time, DDP and MTX, singly, seem to induce the largest number of responses, while VLB and ADM, singly, are good secondary agents. The combinations of DDP + ADM, and VLB + MTX appear to be somewhat more effective than the single drug components, and hopefully a four-drug combination may be even more effective. Since significant antitumor activity is achieved with the drugs now available, we plan to initiate a randomized phase-III study in patients with stage-D tumors after preoperative irradiation and radical cystectomy with lymph node dissection. The data at Memorial Sloan-Kettering Cancer Center indicate a 70% death rate at 1 year, and 87% at 2 years, despite radiation therapy and cystectomy; for such cases, therefore, chemotherapy may be useful in prolonging survival. While new drugs still need to be defined, transitional cell carcinoma of the urothelial tract must be considered a tumor responsive to chemotherapy; we may possibly be on the threshold of chemotherapeutically curative therapies.