Between October 1969 and December 1982, 2,438 patients were enrolled in the National Wilms' Tumor Study and contributed 14,381 person-years of observation to a follow-up study for the occurrence of second malignant neoplasms (SMNs). Fifteen SMNs were observed, whereas 1.77 would have been expected from U.S. incidence rates for 1973-1977 [relative risk = 8.5; 95% confidence interval (CI) = 4.7, 14.0]. Ten years after the Wilms' tumor diagnosis, the cumulative risk of SMN was 1%. The relative risks compared to standard rates were 12/1.11 = 10.8 (95% CI = 5.6, 18.9) for those who received radiation as part of the initial course of treatment and 3/0.60 = 5.0 (95% CI = 1.0, 14.6) for those who did not, but this difference was not statistically significant. Preliminary data suggest that substantial numbers of SMNs occur as patients are followed greater than 10 years from diagnosis.