It has recently been recognized that the ability of insulin to augment blood flow is reduced in insulin-resistant conditions such as obesity and noninsulin-dependent diabetes mellitus. Normal aging is characterized by resistance to insulin-mediated glucose uptake. We undertook the following studies with the hypothesis that the resistance to insulin-mediated glucose uptake that occurs with aging is caused in part by a reduction in insulin-mediated blood flow. These experiments were conducted on healthy young (n = 13; age, 24 +/- 1 yr; body mass index: 22.2 +/- 0.6 kg/m2) and old (n = 13; age, 77 +/- 1 yr; body mass index: 24.2 +/- 0.5 kg/m2) subjects. Each subject underwent two studies. In the control study, saline was infused for 4 h. In the euglycemic clamp study, insulin was infused for 4 h at a rate of 40 mU/m2.min in the young subjects and 34 mU/m2.min in the old subjects. Blood samples were taken, and calf blood flow was measured using venous occlusion plethysmography at regular intervals in each study. Basal calf blood flow was lower in the elderly (young subjects: 1.51 +/- .08 mL/100 mL tissue per min; old subjects: 1.15 +/- 0.07 mL/100 mL tissue per min, P < 0.002). During the euglycemic clamp studies, steady-state insulin and glucose values were similar in the two age groups. Glucose disposal rates were significantly higher in the young subjects (P = 0.01 by analysis of variance). Mean arterial pressure values were significantly higher in the elderly (P < 0.001 by analysis of variance) throughout the clamp, but there was no significant change over time in either age group. The mean incremental blood flow rate at steady-state (180-240 min) was significantly higher in the young subjects (0.76 +/- 0.23 mL/100 mL tissue per min) than in the old subjects (0.05 +/- 0.09 mL/100 mL tissue per min, P < 0.01). There was a significant correlation between steady-state glucose disposal rate values and incremental blood flow rates in the young subjects (r = 0.59, P < 0.05) but not in the old subjects (r = 0.21, P = NS). We conclude that normal aging is characterized by an impairment in the ability of insulin to modulate blood flow, which may contribute in part to the insulin resistance of aging.