An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the B beta-fibrinogen -455 G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease. The purpose of this study was to investigate the influence of the beta-fibrinogen -455 G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the B beta-fibrinogen -455 G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the -455 A allele compared to subjects with the -455 GG genotype. This association did not exist in women carrying the fibrinogen -455 A allele. The -455 GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the -455 GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the B beta-fibrinogen -455 A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia and a functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.