By examining sequence similarity between the V3-loop of gp120 from various HIV-1 isolates and human proteins, we found that the V3 loop portion KKGIAIGPGR in strain New York 5 (HIV-1NY5) shares 70% identical residues with the collagen-like region (CLR) of human complement component C1q-A. C1q CLR was found to react with autoantibodies from several autoimmune disorders. Thus, we assumed that it would be of interest to find out the C1q reactivity with antibodies from AIDS sera. The results obtained show that the V3 loop-derived synthetic peptide KKGIAIGPGRTLY reacts both with AIDS patients sera and with antibodies purified on the V3 loop peptide-affinity column. The same affinity-purified antibodies bind also to C1q molecules. Since, according to our previous results, HIV-1 V3 loops and immunoglobulin heavy chain variable regions (Ig VH) share several common features, we suggest that the envelope of HIV-1NY5 bears a functional internal image of the C1q-A CLR epitope. Therefore, gp120 could manipulate the immune network and contribute to HIV-induced autoimmunity.