In some children with bilateral Wilms' tumor, reduction of tumor burden cannot be accomplished without total nephrectomy. In Denys-Drash syndrome, nephrectomy is required for associated Wilms' tumor or after progression to end stage renal disease secondary to diffuse mesangial sclerosis because of risk of development of Wilms' tumor. Current recommendation is to wait at least 1-2 yr after completion of chemotherapy for Wilms' tumor before renal transplantation. The North American Pediatric Renal Transplant Cooperative Study dialysis (1992-2001) and transplant registries (1987-2002) were analyzed, comparing children 0-18 yr old with Wilms' tumor and Denys-Drash syndrome to other primary diagnoses. There were 37 children with Wilms' tumor and 33 with Denys-Drash syndrome in the dialysis registry. Of these, 10 children with Wilms' tumor and three with Denys-Drash syndrome did not receive a renal transplant and all died. The cause of death was Wilms' tumor in eight children with Wilms' tumor and in one with Denys-Drash syndrome. The transplant registry included 43 children with Wilms' tumor, 43 children with Denys-Drash syndrome, and 7469 patients with other diagnoses. Acute rejection, graft and patient survival profiles from all three groups at 6 months, 1 and 3 yr post-transplant were comparable. There were no graft failures or deaths because of recurrent Wilms' tumor in the Drash group. There was one death with Wilms' tumor in the Wilms' group - a 2.5-yr-old child transplanted after 6 months of dialysis who died of Wilms' <6 months after renal transplantation. In conclusion, most children dialyzed because of Wilms' tumor and Denys-Drash syndrome who did not receive a renal transplant died of Wilms' tumor. However, the outcomes of children with Wilms' tumor and Denys-Drash syndrome who proceeded to renal transplantation are comparable with children with other diagnoses, with no graft failures because of recurrence and only one death from Wilms' tumor in a Wilms' patient who received only a short course of dialysis prior to transplantation. Current practices in children with Wilms' tumor and Denys-Drash syndrome appear to be on target to portend good outcome following renal transplantation.