One-hundred-eighty-eight children up to 16 years of age were randomized in the second National Wilms' Tumor Study (NWTS) with tumors that were confined to the kidney and that had been totally excised (Group I). Most fared well whether treated for six or for 15 months with both actinomycin D (AMD) and vincristine (VCR). No postoperative radiation therapy (RT) was given. The two-year relapse-free survival (RFS) and two-year survival rates were 88 and 95%, respectively. Two-hundred-sixty-eight randomized patients with more advanced local lesions (Groups II and III) and 57 with distant metastases (Group IV) had postoperative RT and were scheduled for 15 months treatment with either AMD and VCR (Reg. C) or AMD plus VCR plus Adriamycin (Reg. D). The 77% two-year RFS rate for Reg. D was significantly different from the 63% with Reg. C. As in the first NWTS, patients with tumors of unfavorable histology (UH) had a significantly worse prognosis than those with favorable histology (FH), as did those with positive nodes. Survival rates at two years were 54% for UH vs. 90% for FH, and 54% vs. 82% for those with and without lymph node involvement.