Children infected with the human immunodeficiency virus (HIV) have T helper cell deficiency, but frequent bacterial infections suggest phagocyte dysfunction. Whole blood chemiluminescence (CL) assays were used to measure the respiratory burst capacity of phagocytes from HIV-infected children, perinatally HIV-exposed but uninfected children, and normal healthy children. Phagocytes were stimulated by zymosan opsonized with human complement with and without priming by platelet-activating factor (PAF) or FMLP. Activities of enzymes involved in the respiratory burst, oxidase and myeloperoxidase, were examined after opsonin receptor-independent stimulation with PMA. Unprimed CL responses to opsonized zymosan were decreased for HIV-infected children with severe CD4 lymphocyte suppression compared with healthy children (P=.03), and PAF-primed CL responses to opsonized zymosan were decreased in HIV-infected children with both moderate and severe CD4 lymphocyte suppression (P=.02 and P=.01, respectively), despite normal or increased activities of the respiratory burst enzymes. These impairments may contribute to secondary bacterial infections.