Caloric restriction (CR) initiated in young rodents has been thoroughly documented to enhance longevity, but its efficacy when introduced at older ages has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1 hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented with corn oil and sweetened condensed milk (S). The C control rats were fed ad libitum, R rats were restricted to 32% of the caloric intake of the controls, and S rats were allowed to consume not more than 8% more calories than C rats. After 6 weeks, the average weights were significantly different between all diet and age groups. Although calorie manipulation altered body weight, no significant effect of the dietary intervention on longevity was found. The average lesion burden, including tumor burden and prevalence of nearly all commonly occurring lesions, were comparable between the groups. Thus, the manipulation of weight at ages beyond middle age has a much less profound impact than similar interventions during growth and maturation in rats.