To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4⁺ T cells. Polyclonal peripheral blood CD4⁺ cells were costimulated ex vivo and subjects were given infusions of up to 3 × 10¹⁰ activated CD4⁺ cells. Dose-dependent increases in CD4⁺ cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4⁺CCR5⁺ cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4⁺Ki-67⁺ cells increased whereas CD4⁺ T cells containing T cell–receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T-cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection.