Adenylate cyclase toxin (CyaA) is produced by Bordetella pertussis, the causative agent of whooping cough. CyaA specifically binds to the heavily Nglycosylated β2 integrin receptor CD11b/CD18 on its main cellular target myeloid phagocytic cells. However, CyaA can also interact with and intercalate into cell membranes lacking CD11b/CD18, where saccharides may play a propagating role in membrane binding. The present study was undertaken to examine whether CyaA can bind to ganglioside GM1 (GM1), a membrane raft associated oligosaccharidebearing lipid. For this sake, the potency of highly selective GM1 ligand cholera toxin subunit B (CTB) to block CyaA binding in GM1-positive CD11b/ CD18-negative human erythrocytes and K562 cells was studied by flow cytometry. Pre-treatment of erythrocytes and K562 cells with CTB markedly (29% and 28%, respectively) decreased their binding of CyaA, indicating that CyaA can bind to GM1, apparently by recognizing terminal galactose and sialic acid residues in GM1.