Patients with advanced transitional cell cancer of the bladder, urethra, or renal pelvis were treated with a combination of cyclophosphamide, doxorubicin, and cisplatin. Fifteen patients were evaluated, 12 of whom had cancer of the urinary bladder. Metastatic sites were bone (47% of the patients); lung (33%) pelvis (27%); liver (20%); nodes (7%); and brain (7%). Only two patients (13%) achieved a partial response (in measurable node and lung lesions) and survived 16 and 58 weeks. Three patients (20%) had minor responses (in measurable bone, pelvis mass, and bone and local lesions) and survived 8, 28, 102+ weeks, respectively. Four patients had stable disease and six had disease progression, with a median survival of 4 weeks. Overall toxic effects were leukopenia (53% of the patients); thrombocytopenia (27%); nausea and vomiting (67%); alopecia (60%); and renal (13%). We concluded that the response rate to the combination of cyclophosphamide, doxorubicin, and cisplatin in transitional cell cancer of the urothelium was not superior to the reported response rate ot a single agent (eg, cisplatin), and toxicity was greater.