During the development of the immune system, a restricted set of VHgene segments provides the bulk of the immunoglobulin heavy chain repertoire. Most of these VHgenes 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 VHfamilies, and more specifically one single VHgene contributes to a large extent to the adult autoimmune repertoire in restricted as well as unrestricted responses. This VHgene segment is not particularly overexpressed in the fetus. Since the only common element to these autoreactive responses is the region encoded by the VHgene itself, these observations may provide an important insight into B-cell regulation.