In recent years our laboratory has developed an immunological hypothesis for the pathogenesis of atherosclerosis. We have shown that cellular and humoral immune reactions against heat shock proteins (Hsps) 60/65 expressed on the surface of stressed endothelial cells comprise the initial event in the pathogenesis of this disease. In the course of these studies, we also investigated normal, unaffected arteries for control purposes (carotid bifurcations from children aged 8 weeks to 10 years). This investigation led to the unexpected and previously unknown finding that mononuclear cells pre-exist in the intima at bifurcation sites. Our findings can be summarized as follows: Mononuclear cells are always found in the intima, primarily at sites subjected to major hemodynamic stress. Although the proportion of macrophages vs CD3(+) T-cells differs, overall the latter clearly predominate. Most of the T-cells express the T-cell receptor (TCR)alpha/beta, but TCRgamma/delta cells are also present. We also identified dendritic cells and mast cells in the intima. Analogous to the mucosa-associated lymphoid tissue (MALT) we coined the designation "vascular-associated lymphoid tissue" (VALT) for these newly discovered cellular aggregates in the arterial intima.