To test the hypothesis that glycemic sensitivity to epinephrine is reduced in older individuals and to assess the impact of a sedentary lifestyle on responses to the hormone, we performed 30-min sequential intravenous infusions of epinephrine (0, 41, 82, 164, 246, and 328 pmol · kg¹ · min¹) in young (n = 10) and older (n = 23) healthy subjects. We performed these again after 12 mo of physical training, which raised peak O₂ consumption from 24.4 ± 1.0 to 30.4 ± 1.4 ml · kg¹ · min¹ (P < 0.01) in most of the older subjects (n = 21). During epinephrine infusions, plasma epinephrine concentrations were higher (P = 0.0001) in older than in young subjects (e.g., final values of 7,280 ± 500 vs. 4,560 ± 380 pmol/l, respectively), indicating that the clearance of epinephrine from the circulation was reduced in the older individuals. Plasma epinephrine concentration-response curves disclosed reduced glycemic sensitivity to the hormone in the older subjects (P = 0.0001), a finding plausibly attributed to increased sympathetic neural activity, as evidenced here by higher plasma norepinephrine concentrations (P = 0.0001) in the older subjects and consequent desensitization of cellular responsiveness to catecholamines. Training did not correct reduced epinephrine clearance, reduced glycemic sensitivity to epinephrine, or raised norepinephrine levels. We conclude that aging is associated with reduced clearance of epinephrine from the circulation and reduced glycemic sensitivity to epinephrine, the latter plausibly attributed to an age-associated increase in sympathetic neural norepinephrine release. These age-associated changes are not the result of a sedentary lifestyle.