GLUT3 glucose transporter gene expression is confined to neurons, while GLUT1 gene expression is limited to endothelial cells in normal brain. Thus far, neither of the GLUT genes has been shown to be consistently expressed in glial cells in adult brain in vivo under normal conditions. However, GLUT gene expression may be aberrant in human brain glial tumors. The present investigation shows that the GLUT1 and GLUT3 transcripts are differentially expressed in a series of 20 human brain tumors. The GLUT1/actin mRNA ratio increased in parallel to the astrocytoma grade, compared to a control human brain cortex, although no change in this ratio was seen in 5 meningiomas. Immunoreactive GLUT1 protein was not detectable in human brain tumors, including high-grade gliomas. Both 4.2 or 2.7 kb GLUT3/actin mRNA ratios showed a linear correlation with the glioma grade (P < 0.025), and the GLUT3-immunoreactive protein was also expressed in high grade gliomas. These studies provide evidence for induction of GLUT1 and GLUT3 gene expression in malignant glial cells, and the mRNA levels correlate with the biologic aggressiveness of the tumor. The detection of immunoreactive GLUT3, but not GLUT1, in the high grade gliomas suggest the GLUT3 isoform may be the predominant glucose transporter in highly malignant glial cells of human brain.