In rats fed ad libitum, the fat cell number increases with advancing age; the temporal pattern of this increase differs in the perirenal depot compared with the epididymal depot. Restriction of energy intake reduces the number of fat cells in fat depots whether the restriction is started soon after weaning or in adult life. The capacity for diet to modulate fat cell number is maintained through most, if not all, of the life span. Restriction of energy intake delayed death due to neoplasms; restriction of dietary fat or protein without restriction of energy did not have this action. In the case of leukemia/lymphoma, the data indicated that it was the age of occurrence that was delayed by the restriction of energy intake. Because restriction of dietary energy maintains most physiologic systems in a youthful state and retards a broad spectrum of disease processes, the importance of its effects on cellularity and cell proliferation in its anti-aging action remains to be established.