The influence of dietary components on the occurrence of, and mortality from spontaneous neoplasms in male F344 rats was investigated. The dietary regimens studied included restriction of specific dietary components (energy, fat, protein and mineral), as well as different sources of dietary protein (casein, soy protein and lactalbumin). A statistical approach based on contributing causes of death was used to obtain the mortality due to all neoplasms, and the relative onset rate of frequently observed neoplasms, e.g., leukemia, pituitary adenoma, testicular interstitial cell tumor, etc. Only the regimen involving energy restriction reduced the mortality due to all neoplasms. Neither reduction of individual components without energy restriction, nor replacement of casein with soy protein or lactalbumin as the protein source affected mortality. Analyses of the relative onset rate of selected neoplasms also indicated that only a reduction of energy intake suppressed the occurrence of most of these neoplasms. Other dietary regimens, at most, suppressed a few types of neoplasm. It is concluded that a reduction in energy intake is a key dietary factor for the prevention of neoplastic diseases in rats.