Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of atherosclerotic processes. To contribute to the analysis of the genetic background of atherosclerosis we searched for DNA polymorphisms in the genes encoding adhesion molecules especially E-selectin which seems to be expressed only in activated endothelium. An adenine to cytosine substitution for cDNA position 561 resulting in an amino acid exchange from serine to arginine (position 128) was detected in the epidermal growth factor like domain. A significantly higher mutation frequency (P = 0.02) was observed in 97 patients aged 50 years or less with angiographically proven severe atherosclerosis (allele frequency of arginine 0.155) compared with an unselected population (allele frequency of arginine 0.088) as well as in 40 patients aged 40 years or less (allele frequency of arginine 0.21, P = 0.0025). These data suggest that the 128-serine/arginine polymorphism is associated with a higher risk for early severe atherosclerosis.