Twenty-one patients with advanced Wilms' tumor entered a phase II study with high-dose ifosfamide (3 g/m2 over two days every 15 days). Mesna and hyperhydration were associated with minimal bladder toxicity. After two courses, five partial responses and six complete responses were observed. Ten patients did not respond. The median duration of response was 2 months (range, 1 to 7). Therapy was delayed because of leukopenia for 1 or 2 weeks in only three cases. Fever and infection were not observed. Seven patients presented with hematuria, three of whom were among the 17 patients coadministered mesna, which did not interfere with subsequent therapy.