Activity has been demonstrated for both single agents and combination chemotherapy in advanced transitional cell carcinoma of the uroepithelium. Regimens are palliative; duration of response has been modest, usually ranging from 3 to 8 months. There are few complete responders; occasional patients remain disease-free at 1 and 2 years. Among the single agents, cisplatin (33% response rate in 188 patients thus far reported in the literature) and methotrexate (29% response rate) are among the best studied and perhaps most active single agents. Substantial activity is also seen for cyclophosphamide (31%), doxorubicin (23%), 5-fluorouracil (35%), and mitomycin C (21%). VM-26 and vincristine appear to have activity, but relatively few patients have been treated. Response rates to combination chemotherapy, including cisplatin + doxorubicin, cisplatin + cyclophosphamide, and cisplatin + doxorubicin + cyclophosphamide, have ranged from 12% to 78%. Non-platinum-based combination regimens have also been studied, with response rates ranging from 14% to 50%. The large number of active agents, together with the occasional occurrence of a relatively durable complete response, raises hopes that more active combinations will be found and that the current surgical adjuvant trials will be positive in this disease.