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Our objective was to measure the early dynamics, evolution, and durability over 96 wk of immunologic responses in children receiving their first highly active antiretroviral therapy (HAART) regimen. The study was designed as a prospective, single-arm study. Twelve human immunodeficiency virus (HIV)-infected children (median age, 11.8 yr) were enrolled. All subjects received stavudine, nevirapine, and ritonavir. Serial measurements included HIV viral load, lymphocyte subsets, thymic volume by computed tomography (CT), neurocognitive testing, and brain CT. Baseline median CD4⁺ T cell count was 589 cells/mm³ , viral load was 3.9 log₁₀ HIV RNA copies/mL, and thymic volume was 16.3 cm³ . Ten children had an undetectable viral load at week 48. Eight maintained an undetectable viral load at 96 wk. The median increase in absolute CD4⁺ T cell count was 225 cells/mm³ by week 48, and 307 cells/mm³ by week 96. The median increase in naive (CD45RA⁺ CD62L⁺ ) CD4⁺ T cells was 133 cells/mm³ by week 48, and 147 cells/mm³ by week 96. The median number of naive CD8⁺ T cells increased from 205 to 284 cells/mm³ by week 24; this increase was sustained to week 96. The number of B cells increased and was associated with a decrease in immunoglobulin levels. The number of natural killer cells was stable. There were no significant changes in thymic volume. Most children exhibited stable cognitive function over the course of the study. We conclude that, in this cohort of relatively immunocompetent HIV-infected children, an initial HAART regimen was associated with rapid and sustained increases in total CD4⁺ T cells, in naive CD4⁺ and CD8⁺ T cells, and in B cells through 96 wk.