Caloric restriction (CR) appears to affect aging by the inhibition of the specific chronic diseases which occur at increasing frequency with age. A common disease in F-344 rats, granulocytic leukemia, appears to have a window where it is sensitive to the effects of CR. Other diseases, such as pituitary adenomas, appear to have a different relationship to growth in the animal. Additionally, a model for the major disease for a number of long-lived strains of mice, lymphoma, which CR effects by inhibiting the expression of the causative agent, is being developed. Evaluation of the effects of CR on neoplasia, degenerative disease and physiological parameters suggests that the major factors in expression of these diseases is the alteration of growth factors, hormonal status, etc., and that these alterations also affect strain-specific pathologies depending on when they are changed in the life span. Effecting different diseases at different times in the life span, long-term CR, by limiting exposure to endogenous growth factors, altering physiological characteristics, and limiting exposure to food toxicants, inhibits the onset of disease, and its sequela, aging.