The contributions of insulin (IRI), glucagon (IRG), and corticosterone production to the glycemic changes associated with age and starvation were examined in 3 and 6 month old ob/ob and lean mice. Three month old ob/ob mice had elevated glucose levels under all feeding conditions, but in older obese mice basal hyperglycemia was evident only after 48 hours of food deprivation. These age differences in glycoregulation were not consistently related to changes of IRI, IRG, or corticosterone concentrations. Similarly, the mild diabetes associated with senescence in lean mice was only evident during food deprivation. This abnormality in glycoregulation was also independent of decreased IRI or elevated diabetogenic hormone concentrations. Our results indicate that there is no simple hormonal basis for the partial remission of diabetes in older ob/ob mice, or for the development of mild diabetes in aging lean mice. Additionally, these data suggest that the tissue 'resistance' that is associated with chronic insulin overproduction might also develop in response to persistent overproduction of other metabolically-active hormones.