BACKGROUND: There are few data describing the specificity, breadth and magnitude of T cell responses to HIV-1 in infancy. METHODS: HIV-specific CD8+ and CD4+ T cell responses to peptide pools representing Gag, Env, Pol, Nef and the regulatory regions (Reg) were simultaneously measured in 18 perinatally-infected infants and 14 of their chronically-infected mothers, using a whole blood interleukin-2 and interferon-gamma flow cytometric intracellular cytokine staining assay. RESULTS: HIV-specific CD8+ T cell responses were detected in all the infants aged 6 weeks and older (range 0.1-6.62%) and their mothers (range 0.1-4.89%). HIV-specific CD4+ T cell responses were detected in 33% of the infants (range 0.11-0.54%) and 73% of the mothers (range 0.16-0.84). CD8+ T cell responses in the mothers were almost equally spread between the variable (Nef, Reg and Env) and conserved proteins (Gag and Pol). Conversely, CD8+ T cell responses to the more variable proteins dominated in the perinatally-infected infants comprising 74% of the total response. Interestingly, mothers and infants shared responses to at least one peptide pool, whereas only one mother-infant pair shared a peptide pool targeted by CD4+ T cells. Two in-utero-infected infants tested at birth had CD8+ T cell responses, and one of them had an Env-specific CD4 T cell response. CONCLUSION: Our observations that HIV-specific CD8+ and CD4+ T cell responses can be detected in perinatally-infected infants from 6 weeks of age and that CD8+ T cell responses predominantly target the variable proteins have important implications for HIV vaccine design.