During the development of the immune system, a restricted set of V_H gene segments provides the bulk of the immunoglobulin heavy chain repertoire. Most of these V_H genes have been found later in life encoding autospecificities either in normals or in patients with autoimmune diseases. Additionally, there is considerable evidence that the fetal/neonatal B-cell repertoire is autoreactive and idiotypically connected. In the course of sequencing the heavy chain of a panel of human autoantibodies mainly derived from patients with autoimmune diseases, we found that one of the V_H families, and more specifically one single V_H gene contributes to a large extent to the adult autoimmune repertoire in restricted as well as unrestricted responses. This V_H gene segment is not particularly overexpressed in the fetus. Since the only common element to these autoreactive responses is the region encoded by the V_H gene itself, these observations may provide an important insight into B-cell regulation.