It is well established that dietary caloric restriction (CR) can retard aging in mice, but it is less clear whether CR can exert similar effects in long-lived species, such as primates. To examine this possibility, we tested the effect of CR on dehydroepiandrosterone sulfate (DHEAS), a reliable endocrine marker of aging in both human and nonhuman primates. Because DHEAS is known to decline markedly during aging, we predicted that the plasma concentrations of this adrenal steroid would be significantly higher in the CR animals than in the age-matched controls. The study included six young (~10 years) and ten old (~25 years) male rhesus macaques (Macaca mulatta), approximately half of the animals in each age group having undergone >4 years of 30% CR. Each animal was fitted with a vascular catheter, which enabled hourly blood samples to be remotely collected for 24 hours, without resorting to the use of anesthesia. Radioimmunoassay of DHEAS, as well as cortisol (another adrenal steroid), revealed a pronounced diurnal plasma pattern for both hormones, with peaks occurring in late morning (lights on from 7:00 h 19:00 h). As expected, plasma DHEAS (but not cortisol) concentrations showed a marked aging related decline. More importantly, however, plasma DHEAS concentrations were not significantly higher in the CR animals than in the age matched controls. Taken together, these data emphasize that in male rhesus macaques plasma concentrations of both DHEAS and cortisol have a diurnal pattern. However, the data fail to support the hypothesis that CR can prevent the aging associated decline in plasma DHEAS concentrations. Whether initiation of CR earlier in life, or exposure to a longer period of CR, can produce a more pronounced effect remains to be determined. (Supported by NIH Grants RR 00163, RR 14451 & AG 19914.-19914).