Removal of the vWF intron 1 sequence abolishes endothelial cell expression of vWF protein. Replacement of the intron 1 sequence with intron 2 from the mouse Down syndrome critical region gene or intron 6 from hagfish factor X restores vWF protein expression by endothelial cells. Expression of vWF by megakaryocytes does not require the same intron 1 splicing event.