We evaluated the diagnostic utility and prognostic value of immune-complex-dissociated (ICD) HIV-1 p24 antigen detection in a prospective cohort study of perinatally acquired HIV-1 infection in Butare, Rwanda. HIV-1 p24 antigen was measured after acid dissociation in plasma samples collected at 6 weeks and 3 months of age from 36 HIV-1 infected and 80 uninfected children born to HIV-1 infected women. Among children with persistent HIV-1 antibody after 12 months of age, 26.7% of samples tested ICD HIV-1 p24 antigen positive. Among children who died between 3 and 12 months of age but were classified as HIV-1 infected, 17.6% tested p24 antigen positive at 6 weeks of age and 33.3% at 3 months of age. Female infants were more likely to test p24 antigen positive than male infants (p = 0.046). The specificity of the assay was 96.8%. Cumulative probabilities of child survival to 36 months of age were computed by HIV-1 status of the child and early p24 antigenemia. The mean survival time was 7 months for HIV-1 infected children with a high (> 50 pg/ml) p24 antigen concentration versus 20 months for children with p24 antigen concentrations between 10 and 50 pg/ml (p = 0.02). Cumulative probabilities of survival to 36 months of age were 0% among HIV-1 infected children with at least one positive p24 antigen test, 44% among confirmed HIV-1 infected children who were p24 antigen-negative at both 6 weeks and 3 months of age, and 95% among seroreverting children (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)