There is increasing evidence that autoimmune phenomena play an important role in the immunopathogenesis of AIDS. We found a high degree of sequence homology between HIV-1 and antigen receptor molecules, immunoglobulins and T cell receptors. Based on recent findings that the appearance of anti-Fab autoantibodies and attachment of gp120/immunoglobulin/complement complexes on CD4+ T cells are associated with the decrease of CD4+ T cells in HIV-infected patients, we hypothesize herein that cross-reactive anti-F (ab')2 autoantibodies and circulating gp120 molecules are responsible for a destabilization of the immune network and the elimination of CD4+ T cells.