The metabolic basis for the reduced glucose tolerance that occurs during aging in humans has been explored with the aid of a primed constant intravenous infusion method of labeled glucose (6-3H; 6,6,2H- and U-13C-glucose). Healthy young adult men and women (24 +/- 3 yr) and elderly men and women (75 +/- 4 yr) participated in a series of studies designed to quantify rates of plasma glucose appearance, oxidation, and recycling while subjects were in the postabsorptive (basal) state and to determine rates of hepatic glucose production and glucose disappearance in response to intravenous glucose at approximately 1 and 2 mg x kg-1min-1 and also 4 mg x kg-1min-1 without or with a simultaneous infusion of insulin to maintain normoglycemia. Basal rates of glucose production were 2.41 +/- 0.06 and 2.18 /+/- 0.05 mg x kg-1min-1 in the young adults and elderly, respectively (P less than 0.05). Recycling of glucose carbon and glucose oxidation rates did not differ significantly between the two age groups. Infusion of unlabeled glucose reduced hepatic glucose production to the same extent in the two groups, indicating that the mechanisms responsible for altered hepatic glucose production with intravenous glucose administration remain intact during human aging. Plasma insulin changes were similar in young adult and elderly subjects receiving 4 mg x kg-1min-1 unlabeled glucose except that the higher plasma glucose levels in the elderly were associated with higher insulin levels. For elderly subjects, the amount of exogenous insulin required to maintain normoglycemia at the 4 mg x kg-1min-1 glucose infusion rate was about twice that necessary in young adults.