The influence of replacing dietary casein with soy protein on longevity and age-related pathologic lesions of male Fischer 344 rats was investigated. Caloric intake and body weights were similar for rats on the two diets. Rats on the soy protein-containing diet had a median length of life of 844 days compared to 730 days for those on the casein-containing diet (p less than .002), and the ages of the 10th percentile survivors were 937 and 857 days, respectively (p less than .02). The progression of chronic nephropathy was markedly retarded by replacing casein with soy protein. Only 7% of the rats dying spontaneously on the soy protein-containing diet exhibited end-stage chronic nephropathy compared to 41% of the rats on the casein-containing diet. Clearly, the soy protein-containing diet enables ad libitum fed male Fischer 344 rats to be used as a model for aging research without the occurrence of renal failure as a major confounding problem.