Patients with the Denys-Drash syndrome (Wilms' tumor, genital anomalies, and nephropathy) have been demonstrated to carry de novo constitutional mutations in WT1, the Wilms' tumor gene at chromosome 11p13. We report three new cases, two carrying a previously described WT1 exon 9 mutation and one with a novel WT1 exon 8 mutation. However, unlike patients in previous reports, one of our three patients inherited the affected allele from his phenotypically unaffected father. This observation indicates that the WT1 exon 9 mutation affecting 394Arg demonstrated in over one-half of the patients with the Denys-Drash syndrome may exhibit incomplete penetrance. Consequently, familial studies in patients affected by this syndrome are recommended.