To determine the sensitivity and specificity of anti-human immunodeficiency virus (HIV) IgA in identifying infected infants at or before 6 months of age among the offspring of HIV-infected mothers.Prospective comparison of anti-HIV IgA measurement performed in 2 different laboratories by 2 different methods with the criterion standard of blood culture.Five centers in the United States and Puerto Rico.Population-based sample of 156 infants of HIV-infected mothers in the Women and Infants Transmission Study.Results of anti-HIV IgA test in relation to the infection status of the infants as measured by blood culture.Six-month plasma or serum samples were first tested in the 2 laboratories. The sensitivity and specificity of anti-HIV IgA in detecting infected infants at this age by laboratories 1 and 2 were 69% and 63% and 100% and 99%, respectively. A look-back study of samples obtained at birth, 1, 2, and 4 months was then performed on all infected children and a matched set of uninfected children. The performance of the test at birth was unsatisfactory in both laboratories (sensitivity 44% and 33%, specificity 43% and 60%), whether peripheral or cord blood was examined. At 1, 2, and 4 months, the sensitivity of the test was lower than at 6 months, but specificity was high. A modest correlation of absent anti-HIV IgA antibody and low percentage of CD4 cells in peripheral blood was seen at 6 months of age.The anti-HIV IgA test has moderate sensitivity and high specificity for the diagnosis of HIV infection at 6 months of age in the offspring of infected mothers.