The interferon-g ELISPOT assay was used to assess and compare the magnitude and breadth of human immunodeficiency virus (HIV)–specific CD8 T cell responses in treatment-naive subjects during the first year of HIV primary infection and during the chronic phase of infection. Twenty-five subjects tested within a year of exposure to HIV resulting in seroconversion and 20 subjects with chronic infection were screened for HIV peptide–specific activity by stimulating peripheral blood mononuclear cells with a panel of 5–21 HLA class I–restricted HIV peptides (mean, 11.2 ^ 3.5 HIV peptides). There was a significant correlation between the magnitude and breadth of HIV-specific effector responses and time elapsed from exposure (r ¼ 0.63 for magnitude vs. time and r ¼ 0.64 for breadth vs. time; P , .02, paired t test). Maximal breadth of the HIV gene product reactivity was achieved within 2 months of exposure for Nef-specific responses and by 4 months of exposure for responses directed to Env, Gag, and reverse transcriptase.