There has been concern about the suitability of the male Fischer 344 (F344) rat as a model for aging research because of the high prevalence of a single disease, severe nephropathy, at advanced ages which confounds the interpretation of an aging study. In a publication from our laboratory, Iwasaki et al. (1988) reported that replacing the casein in our standard semisynthetic diet with soy protein markedly decreases the progression of nephropathy with advancing age in ad libitum fed male F344 rats. In the present study, it is shown that replacing the casein with lactalbumin does not decrease the occurrence of severe nephropathy in ad libitum fed rats. It is also shown that dietary restriction (DR) studies can be effectively executed in the male F344 rat when soy protein is the source of dietary protein. It is further shown that when the energy intake of the rats fed soy protein-containing diets was reduced to 60% of the ad libitum intake, almost one-third of the rats died with an absence of severe morphologic lesions, that is, lesions which contribute to the death of the rat. It is concluded that the male F344 rat is an excellent model for aging research when soy protein is the source of dietary protein; no single disease process was found to be primarily responsible for death with such a diet.