Friedreich's Ataxia (FA) is a neurologic disorder associated with a high prevalence of diabetes mellitus. To assess insulin secretion and insulin resistance, glucose and insulin responses to oral glucose and insulin binding to circulating monocytes and dextran gradient fractionated and unfractionated red blood cells (RBCs) were compared in 11 subjects with FA to 11 age-matched controls. Glucose and insulin responses were elevated from one to three hours after oral glucose in FA. The mean corrected insulin responses were not different while peripheral insulin activity (A) was significantly decreased (1.38 ± 0.22 v 0.77 ± 0.16, control v FA, P < 0.025) indicating the presence of insulin resistance. A significant correlation between the degree of insulin resistance (A) and duration of neurologic symptoms was found (r = .65. P < 0.025). Resistance to exogenous insulin was confirmed in ten subjects with FA by intravenous insulin tolerance tests (KITT, %/min, 6.25 ± 0.90 v 3.93 ± 0.61, P < .05). Both FA and control groups showed highest insulin binding to fraction A (youngest) RBCs, but no difference was observed between the two groups. However, insulin binding to monocytes was significantly decreased in subjects with FA (% specific binding/10⁷ cells/mL, 6.37 ± 0.71 v 4.51 ± 0.39, P < 0.05, control v FA). This was associated with a decrease in apparent receptor affinity. We conclude that FA is associated with insulin resistance, which increases with the duration of neurologic impairment. The insulin binding to monocytes suggests that the insulin resistance may be partially explained by a receptor defect.