The expression of chemokine receptors on leukocytes is related to their activation state. However, the exact mechanism underlying the induction of each chemokine receptor is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell trafficking and HIV infection, is induced in human T cells. CCR5 was marginally detected on a freshly prepared human peripheral blood mononuclear cell (PBMC) population. Long-term (8-day) stimulation of PBMC with IL-2 resulted in high levels of CCR5 expression on T cells. IL-12 failed to induce CCR5 on T cells in such a directly stimulated PBMC population. Stimulation of PBMC T cells with anti-CD3 plus anti-CD28 induced detectable albeit very low levels of CCR5 along with the induction of IL-12 receptor. However, these TCR-triggered T cells expressed much higher levels of CCR5 when stimulated with IL-12. Although IL-2 also induced CCR5 expression, CCR5 expression was more potent in IL-12 than IL-2 stimulation. These results indicate that, in addition to IL-2, IL-12 plays an important role in the induction of CCR5 expression on T cells, particularly TCR-triggered T cells.