The intracarotid injection method has been utilized to examine blood-brain barrier (BBB) glucose transport in hyperglycemic (4-6 days) mice. In anesthetized mice, Brain Uptake Indices were measured over a range of glucose concentrations from 0.010-50 mmol/l; glucose uptake was found to be saturable and kinetically characterized. The maximal velocity (Vmax) for glucose transport was 989 +/- 214 nmol.min-1.g-1. and the half-saturation constant estimated to be 5.80 +/- 1.38 mmol/l. The unsaturated Permeability Surface area product (PS) is = 171 + 8 microliters.min.-1.g-1. A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C-terminal amino acids of the human erythrocyte glucose transporter immunocytochemically confirmed the presence of the GLUT1 isoform in non-obese diabetic (NOD) mouse brain capillary endothelia. These studies indicate that a down-regulation of BBB glucose transport occurs in these spontaneously hyperglycemic mice; both BBB glucose permeability (as indicated by PS product) and transporter maximal velocity are reduced (in comparison to normoglycemic CD-1 mice), but the half-saturation constant remains unchanged.