CD4(+) T helper and CD8(+) cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIV(sf162p3) has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIV(sf162p3), and antigen-specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i. followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia.