Eight human Lewis blood group antibodies were characterized for their fine specificity by the use of specific immunoadsorbents and a kinetic enzyme-linked immunosorbent assay technique. Examination of sera following immunoglobulin fractionation showed IgM anti-Le(a) exhibiting broad cross-reactivity with structures biochemically related to the Lewis antigens. IgG anti-Le(a) binding was restricted to Le(a) and Le(b) These findings are consistent with the concept of affinity maturation of the immune response, which has been previously demonstrated only in animal model systems.