From October 1981 to October 1984, 42 consecutive patients with locally advanced unresectable or metastatic transitional cell carcinoma of the urinary tract were treated with cis-Platinum 50 mg/m2 i.v. and Adriamycin 50 mg/m2 i.v. day 1, and Fluorouracil 500 mg/m2 i.v. and VM26 100 mg/m2 days 1 and 8, every 3 weeks. In the 36 evaluable patients, 4 complete remissions and 15 partial remissions were noted (52.7% response rate). Of the 12 patients with previously untreated, locally advanced bladder carcinoma, 8 responded, with 3 pathologically confirmed complete remissions. Toxicity was moderate. Median survival was 44 weeks. This 4-drug combination had significant palliative activity in our patient population. Its role in the preoperative setting deserves further evaluation.