To investigate whether the effect of ABO blood group on plasma von Willebrand factor (vWF) levels is mediated by the ABH antigenic determinants carried on N-linked glycans of vWF, we studied 158 group A and group O healthy volunteers. vWF antigen (vWF:Ag) and factor VIII antigen (FVIII:Ag) levels were highest in A¹A¹ individuals and higher in A¹O¹ than in A²O¹ or O¹O¹ individuals. Plasma A transferase activity and the amount of A antigen expressed per unit vWF (AvWF) were significantly higher in A¹A¹ than in A¹O¹ individuals and higher in A¹O¹ than in A²O¹ individuals. AvWF was correlated strongly with plasma levels of A transferase activity. Thus, we have clearly demonstrated a direct relationship between ABO genotype, A transferase expression, and the amount of A antigen expressed on circulating vWF. H antigen expression per unit vWF (HvWF) was highest in group O individuals. Among group A individuals, the pattern of HvWF expression was A²O¹>A¹O¹>A¹A¹. In group O and group A²O¹ individuals, HvWF was inversely correlated with plasma vWF levels. In contrast, among group A¹A¹ and A¹O¹ individuals, there was no relationship between AvWF and plasma vWF levels. These findings suggest that it is H antigen expression that mediates the ABO effect on plasma vWF concentration.