It has been suggested that naive immunoglobulins encoded by the V H 3 gene family interact aberrantly with human immunodeficiency virus type 1 (HIV-1) gp120 via a superantigenic epitope, causing initial expansion and eventual depletion of V H 3-expressing B cells. However, this possibility has not been prospectively assessed during an AIDS virus infection. We determined V H family usage in rhesus monkeys during primary infection with chimeric viruses expressing HIV-1 envelopes on a simian immunodeficiency virus (SIV mac) backbone (SHIVs). Four SHIVs with different envelopes and pathogenicities were studied. V H family usage was prospectively assessed in peripheral blood mononuclear cells and lymph node cells of these monkeys by a semiquantitative PCR technique. In the first months following SHIV infection, a period of intense viral antigenemia, representation of various V H families increased or decreased for individual monkeys, but no single V H family was consistently altered. In particular, the average representation of V H 3-bearing B lymphocytes did not change. This observation suggests that the envelope glycoprotein of HIV-1 does not selectively expand or deplete the V H 3 repertoire of primate B cells during acute AIDS virus infection, contrary to predictions of the gp120 superantigen hypothesis.