Cholera is a disease which shows a clear blood group profile, with blood group 0 individuals experiencing the most severe symptoms. For a long time, the cholera toxin has been suspected to be the main culprit of this blood group dependence. Here, we show that both El Tor and classical cholera toxin B-pentamers do indeed bind blood group determinants (with equal affinities), using Surface Plasmon Resonance and NMR spectroscopy. Together with previous structural data, this confirms our earlier hypothesis as to the molecular basis of cholera blood group dependence, with an interesting twist: the shorter blood group H-determinant characteristic of blood group 0 individuals binds with similar binding affinity compared to the A-determinant, however, with different kinetics. (C) 2012 Elsevier Inc. All rights reserved.