To contribute to the analysis of the genetic background of atherosclerosis, especially endothelial dysfunction, we searched for DNA polymorphisms in the genes encoding E-, P-, and L-selectin, and ICAM-I and VCAM-I. We detected 17 mutations by single-strand conformation polymorphisms analysis and direct sequencing. Five of them resulted in an amino acid substitution. In E-selectin, exchanges from serine to arginine (position 128), from leucine to phenylalanine (position 554), and a DNA mutation from guanine to thymine (position 98) present significantly different allele frequencies in young patients with angiographically established, severe atherosclerosis, compared with an unselected population. Results suggest that these polymorphisms are associated with a higher risk for early severe atherosclerosis.