Diphtheria toxin-binding glycoproteins of high molecular weight (>100,000) were identified on the surface of lymph node and thymus cells from hamsters, a diphtheria toxin-sensi Jve species. These diphtheria toxin-binding glycoproteins also interacted with CRM197 protein, which possesses toxin-blocking activity, but not with diphtheria toxoid, fragment A of diphtheria toxin, or cholera toxin, all of which lack toxin-blocking activity. These observations are consistent with the hypothesis that the detected diphtheria toxin-binding glycoproteins are involved in intoxication of cells by this toxin and possibly serve as the plasma membrane receptors for diphtheria toxin.Diphtheria toxin (DT) is produced as a single 63,000-dalton polypeptide chain by Corynebacterium diphtheriae lysogenic for phage P3. Upon