Interleukin-15 (IL-15) enhances the effector mechanisms of anti-HIV immune responses and thus is considered a potential adjuvant of HIV-1 vaccine. However, there are a lack of data concerning the relationships between IL-15 expression and regulation in HIV-1-infected patients and the course of disease progression. We found that IL-15, but not IL-15Rα, is expressed at significantly higher levels in the CD14(+) monocytes [stimulated or not with interferon (IFN)-γ] of long-term nonprogressors (LTNP) than in those of HIV-1 progressors or healthy controls. There was no between-group difference in the amounts of soluble IL-15 released from the cells. We also found that like the healthy controls, the LTNP expressed the IL-15 and IL-15Rα genes in a more coordinated manner than the progressors. Our findings show that there are significant differences in IL-15 expression between patients with different courses of HIV infection, and that the coordinated expression of the IL-15 and IL-15Rα genes is dysregulated in patients with progressive disease. They also provide important information concerning the mechanisms of infection and the potential use of IL-15 as a therapeutic agent.