HIV-specific Elispot responses were investigated in 57 antiretroviral therapy-naive children, of median age 9.9 years. CD8(+) T-cell responses were detected in 96% children; Nef was the immunodominant protein. Responses broadened over time, but there was no association between magnitude, breadth or specificity of response and viraemia. Gag-specific CD4(+) T-cell responses, detectable in 26% children, correlated inversely with viraemia (R = -0.43, P < 0.001), suggesting that preservation of this cell population may be an important goal of therapeutic/vaccine strategies.