The progression of human immunodeficiency virus (HIV) disease and plasma levels of HIV may differ between racial groups. We compared HIV-specific T cell responses between vertically HIV-1-infected Hispanic and African American children. Subjects were matched for sex, age, viral load, and CD4(+) cell count in 18 pairs; T cell responses were measured by cytokine-enhanced interferon- gamma assay. Peripheral blood mononuclear cells were stimulated with HIV consensus peptides from Gag, Nef, and Tat. The influence of ethnicity, sex, age, viral load, and CD4(+) cell count on T cell responses was determined through linear regression analyses. After adjustment for CD4(+) count, age, and log(10) viral load, African American children demonstrated significantly higher Gag responses (average, 486 spot-forming cells higher; P=.01) than Hispanic children; this was significantly driven by robust responses in African American girls near the age of puberty, many of whom carried the human leukocyte antigen class I B*58 allele.