Purpose: Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG). Patients and Methods: Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25- dihydroxycholecalciferol) 0.5 μg/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 μg/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles. Results: The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease- free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks. Conclusion: VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.