Changes in T cell receptor (TCR) V beta repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (SIV). 11 genetically defined rhesus monkeys were experimentally infected with SIVmac or a chimeric simian-human immunodeficiency virus (SHIV), and their peripheral blood lymphocytes (PBL) and lymph nodes were prospectively assessed for TCR V beta gene expression. PBL and lymph nodes of the acutely infected monkeys demonstrated an expansion of selected V beta-expressing T lymphocyte subpopulations as early as 3 d after infection. These expanded V beta-expressing lymphocyte subpopulations were comprised predominantly of CD8+ cells. Six of seven infected monkeys sharing a single electrophoretically defined major histocompatibility complex class I allele exhibited a similar expansion of V beta 14-expressing PBL. Sequence analyses of V-D-J segments of TCR-beta cDNA indicated that the V beta-expressing T cell subpopulation expansion can be oligoclonal. SIVmac-specific CD8+ cytotoxic T lymphocytes were demonstrated in both PBL and lymph nodes of the infected monkeys at the time expansion of the selected V beta-expressing cell subpopulations was seen. Finally, the expansion of the selected V beta-expressing lymphocytes in PBL coincided with the emergence and clearance of SIV p27 from the plasma of the infected monkeys. These results demonstrate that acute infection of rhesus monkeys with SIVmac or SHIV results in an expansion of CD8+ lymphocyte subpopulations expressing selected V beta gene families. The selectively expanded T lymphocytes may contribute to early viral clearance after acute SIVmac or SHIV infection.