IL-12 production is reduced in HIV infection, and recombinant human IL-12 (rhIL-12) augments in vitro HIV-specific proliferative responses in PBMC from HIV-seropositive individuals. To determine whether rhIL-12 could also augment HIV-specific CTL responses we studied 41 HIV-seropositive individuals. Recombinant hIL-12 increased the detectable in vitro HIV-specific CD8 CTL activity of PBMC taken from HIV-seropositire individuals with CD4 counts >500 cells/μl and from some individuals with lower CD4 counts. IL-12 increased cell recovery in cultures of PBMC from HIV-seropositive individuals with CD4 counts >500 cells/μl and also increased the precursor CTL frequency. However, the increase in HIV-specific CTL activity was not due to IL-2 or IFN-γ production or an increase in the number of cells with surface markers characteristic of CTL effector cells. This study demonstrates that rhIL-12 augments in vitro HIV-specific CTL activity and provides evidence to justify further investigation within clinical trials of this cytokine in HIV infection.