There has been no satisfactory animal model for hereditary nephroblastoma (NB; Wilms' tumor), the most common malignant renal tumor in children. A rat subline with a high incidence of NB, designated Upj:TUC(SD)spf.nb, was established from tumor-bearing Upjohn Sprague Dawley (Upj:TUC[SD]spf) stock rats by inbreeding. Incidence of NB was increased from 2.2% (1/46) to 33.0% (4/12) in males and from 10.0% (5/50) to 58.3% (7/12) in females through four successive generations of sister-to-brother mating. The overall incidence of NB-6.5% (14/214) in males and 21.6% (49/227) in females-was over 150-fold higher than the incidence of the tumor in other strains of rats. Of the 63 tumors, 47 (75%) developed at 4 to 12 months of age, and 32 (51%) developed at 7 to 9 months of age. Twelve of the tumors (19%) were bilateral, and in four rats (6.3%) the tumor was triphasic Wilms' tumor. Five of the tumors invaded the adjoining abdominal organs; none metastasized to distant organs. The tumor was consistently transplanted to syngeneic rats through 10 successive passages. The transplanted tumor, as the primary tumor, was composed of blastemoepithelial cells. The Upj:TUC(SD) spf.nb rat with a high incidence of NB, established at the Upjohn Company and donated to the Cleveland Clinic, may be an appropriate animal model for NB (Wilms' tumor) in children.