We have previously shown that the hypersensitivity of KB MDR cells to 2-deoxy-D-glucose is associated with diminished plasma membrane GLUT-1 levels compared with parental, non-MDR cells. Here we report that MDR cells are hypersensitive to the N-linked glycosylation inhibitor tunicamycin, which induces partial inhibition of GLUT-1 glycosylation and diminishes GLUT-1-mediated transport. The effect of tunicamycin, which also enhances the hypersensitivity of MDR cells to 2-deoxy-D-glucose, could not be attributed to alterations in P-glycoprotein activity. The use of agents that act synergistically to diminish the level and activity of GLUT-1 in MDR cells may be of clinical potential. (C) 1997 Elsevier Science Ireland Ltd.