To test the hypothesis that blood-to-brain glucose transport is reduced in poorly controlled type 1 diabetes, we studied seven patients with a mean (± SD) HbA(1c) level of 10.1 ± 1.2% and nine nondiabetic subjects during hyperinsulinemic, mildly hypoglycemic (~3.6 mmol/l, ~65 mg/dl) glucose clamps. Blood-to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves-the latter determined by positron emission tomography (PET)-after intravenous injection of [1-11C]glucose using a model that includes a fourth rate constant to account for regional egress of 11C metabolites. Cerebral blood flow and cerebral blood volume were determined with intravenous H215O and inhaled C15O, respectively, also by PET. At plateau plasma glucose concentrations of 3.6 ± 0.0 and 3.7 ± 0.1 mmol/l, rates of blood-to-brain glucose transport were similar in the two groups (23.7 ± 2.2 and 21.6 ± 2.9 μmol. 100 g-1 min-1, P = 0.569, in the control subjects and the patients, respectively). There were also no differences in the rates of cerebral glucose metabolism (16.8 ± 0.8 and 16.3 ± 1.2 μmol. 100g-1 min-1, P = 0.693, respectively). Plasma epinephrine (1,380 ± 340 vs. 450 ± 170 pmol/l, P = 0.0440) and glucagon (26 ± 5 vs. 12 ± 1 pmol/l, P = 0.0300) responses to mild hypoglycemia were reduced in the patients with type 1 diabetes. We conclude that neither blood-to-brain glucose transport nor cerebral glucose metabolism is measurably reduced in people with poorly controlled type 1 diabetes.