Studies of immune function in human immunodeficiency virus (HIV)-infected children are important, because functional abnormalities can precede CD4+ T-cell loss and are associated with the development of opportunistic and bacterial infections. We sought to correlate clinical parameters and immunological function with HIV RNA plasma levels in 20 children. HIV RNA levels were measured by a polymerase chain reaction assay. We analyzed T-cell responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed [PWM]) and antigens (tetanus toxoid and Candida albicans); T-cell suppressor activity; and humoral immunity to Haemophilus influenzae, hepatitis B, tetanus, and diphtheria vaccines. The median age of the children was 6 years. Eight children had HIV RNA levels less than 200 to 9621 copies per milliliter (group I). Four children had 37,970 to 82,630 copies per milliliter (group II). Eight children had 102,100 to 191,200 copies per milliliter (group III). There were no differences in the HIV-related complications between group I and II children. Group I/II children had significantly higher CD4+ T-cell counts (P = 0.02), less symptomatic HIV disease (P = 0.005), and more detectable protective vaccine immunity (P = 0.014) compared with group III children. Responses to mitogens were conserved in most children. Group I children tended to have higher responses to tetanus toxoid than group II children and significantly higher responses than group III children (P = 0.01). Group I had significantly higher responses to C. albicans than groups II (P = 0.016) and III (P = 0.001). Group I/II children tended to have lower suppressor activity compared with group III children (median, 0 vs 64%). We demonstrated that humoral and cellular immune dysfunction exists at all stages of disease in HIV-infected children but was most severe in children with greater than or equal to 100,000 HIV RNA copies per milliliter. Function was the most intact in children with less than 10,000 copies per milliliter.