Hereditary renal cell carcinoma (RC) in the rat, originally reported by Eker in 1954, is an example of Mendelian dominant predisposition to a specific cancer in an experimental animal. We previously reported that this predisposing inherited gene is a tumor suppressor gene fitting Knudson's "two-hit" model. This study was designed to map the RC susceptibility gene in the Eker rat using backcross animals. Our present data clearly show that the RC gene is genetically linked to the protamine-1 gene (Lod score = 11.65) and the interleukin-3 gene (Lod score = 4.13), both of which are located on the proximal part of rat chromosome 10. Rat chromosome 10 is currently believed to have no syntenic relationship to human chromosome 3p, the presumed site of the putative tumor suppressor gene for human RC and the locus of von Hippel Lindau disease (affected patients develop multiple RCs). Thus, the Eker rat might have a mutation of a novel tumor suppressor gene related to renal carcinogenesis.