CD5+ B cells predominate early in ontogeny and have been associated with autoantibody production. In chronic lymphocytic leukemia (CLL), B lymphocytes express CD5 and frequently produce autoantibodies using developmentally regulated variable (V)-gene segments. Does the self-reactivity observed in CLL reflect transformation of a 'fetal' lineage of cells, or could overexpansion of these B cells occur as a consequence of antigen stimulation? Harry Schroeder and Guillermo Dighiero have reviewed the literature describing antibody sequences in CLL and have compared them with the 'fetal' repertoire. This analysis indicates that CLL cells use a repertoire characteristic of mature cells, and suggests that antigen may play a role in the pathogenesis of this disease.