HIV-I infection affects many of the cellular components vital for the maintenance of immune homeostasis. Similar to the T cell superantigen effect on T cell expansion and depletion in AIDS. HIV components with B cell superantigenic properties could be responsible for the observed B cell activation and skewing of VH family usage. Current data on possible B cell superantigen properties of HIV proteins (gp120) are mostly based on studies describing the clonality and VH family usage of immunoglobulins in HIV infection. Various laboratories reported independently an unusual skewing of the VH-repertoire of antibodies that appears not to be random. According to these observations, an enrichment of VH1 and VH4 family-paralleled a depletion of VH3 family-utilizing anti-HIV-1 gp120 and p24 antibodies in HIV-1 infected individuals and a loss of total VH3+ Ig in patients with late stages of AIDS. Polyclonal and monoclonal (VH1, VH4, and VH5) anti-p24 and gp120 antibodies share a crossreactive idiotype (IF7). IF7 like antibodies were found in the serum of HIV-1 infected individuals, persisting in the course of infection, perhaps contributing to the depletion of VH3 Ig. Furthermore a restriction of clonal heterogeneity of anti-p24 and anti-gp120 antibodies was detected by isoelectric focusing and indicated by skewed kappa/lambda light chain isotype ratios, indicating clonal dominance of certain sets of anti-HIV-1 antibodies during infection. Taken these findings together, a strong case for the involvement of a B cell superantigen can be made, although the mechanism of B cell depletion is not fully understood.