The role played by CD23 in retroviral infections is still unclear. The synergistic effects of interleukin 7 (IL-7) and sCD23 on T cell proliferation and the generation of HIV-1-specific cytotoxic T lymphocytes (CTL) in mitogen- and antigen-stimulated systems were examined. Addition of IL-7 and sCD23 at the onset of culture resulted in a marked augmentation of T cell proliferation and cytotoxic activity. Studies of CTL development in purified mitogen CD8+ T cells demonstrated that IL-7 and sCD23 could act directly on the CD8+ lymphocyte subset to augment cytotoxicity. The data demonstrate that IL-7 and sCD23 synergistically augmented CTL activity independently of IL-2 and IL-12. We analyzed the effects on IFN-gamma production by CD8+ T cells and found that IL-7 alone did not induce detectable levels of IFN-gamma production, but together with sCD23, it synergistically enhanced the production of IFN-gamma. We also found that IFN-gamma appeared not to be required for the enhanced CD8+ CTL activity because rabbit anti-IFN-gamma antibody did not block the synergistic effects of IL-7 and sCD23. These results indicate that IL-7 and sCD23 can exert major upregulatory effects on human CTL development and suggest that these effects are both proliferative and differentiative.