A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV)(1-4). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia(2-5). To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8(+) T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.