Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)-2 therapy results in an expansion of CD4(+) T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NK cells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)-gamma production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56(dim) NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-gamma production were maintained over time. This reconstitution of NK cells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.