Objectives: To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection., Design: Coded serum samples prospectively collected from children born to HIV-infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot., Setting: A university hospital in Baltimore, Md, and an outpatient clinic in Port-au-Prince, Haiti., Population: Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince., Outcome Measures: Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older., Results: The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively., Conclusion: Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries.