Calorie restriction (CR) extends lifespan and reduces the incidence and age of onset of age-related disease in several animal models. To determine if this nutritional intervention has similar actions in a long-lived primate species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% CR in male and female rhesus macaques (Macaca mulatta) of a broad age range. We have observed physiological effects of CR that parallel rodent studies and may be predictive of an increased lifespan. Specifically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory function, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturation. Adult bone mass was not affected by CR in females nor were several reproductive hormones or menstrual cycling. CR attenuated the age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin in males. Although 81% of the monkeys in the study are still alive, preliminary evidence suggests that CR will have beneficial effects on morbidity and mortality. We are now preparing a battery of measures to provide a thorough and relevant analysis of the effectiveness of CR at delaying the onset of age-related disease and maintaining function later into life.