Type 2 diabetes is associated with vascular dysfunction, accelerated atherosclerotic morbidity, and mortality. Abnormal vasomotor responses to chemoreflex activation may contribute to the acceleration of atherosclerotic diabetes complications, but these responses have not previously been investigated. We measured forearm mean blood flow (MBF) and mean vascular conductance (MVC) responses to isocapnic hypoxia in seven healthy and eight type 2 diabetic subjects during local intra-arterial saline infusion and alpha-adrenergic blockade (phentolamine). The effects of hypoxia on saline and phentolamine responses significantly differed between groups; relative to normoxia, the %DeltaMVC with hypoxia during saline was -3.3 +/- 11.2% in control and 24.8 +/- 13.3% in diabetic subjects, whereas phentolamine increased hypoxic %DeltaMVC to similar levels (39.4 +/- 9.7% in control subjects and 48.0 +/- 11.8% in diabetic subjects, P < 0.05, two-way ANOVA). Absolute normoxic MBF responses during saline infusion were 91.9 +/- 21.1 and 77.9 +/- 15.3 in control and diabetic subjects, respectively, and phentolamine increased normoxic MBF to similar levels (165.2 +/- 40.1 ml/min in control subjects and 175.9 +/- 32.0 ml/min in diabetic subjects; both P < 0.05). These data indicate that diabetic and control subjects exhibit similar responses to hypoxia in the presence of alpha-adrenergic blockade despite evidence of exaggerated alpha-mediated vasoconstriction at rest.