The aim of the present study was to explain the observed anergy of Vgamma9Vdelta2 T cells from human immunodeficiency virus (HIV)-positive patients. CD3zeta expression and interferon (IFN)-gamma production by Vgamma9Vdelta2 T cells from HIV-positive and HIV-negative subjects were analyzed. We demonstrated that Vgamma9Vdelta2 T cells from HIV-infected patients expressed a lower level of CD3zeta than did Vgamma9Vdelta2 T cells from healthy donors. A direct correlation was found between CD3zeta expression and IFN-gamma production capability by Vgamma9Vdelta2 T cells. However, activation of protein kinase C by phorbol myristate acetate is able to restore CD3zeta expression and IFN-gamma production. Our findings may contribute to clarification of the molecular mechanisms of Vgamma9Vdelta2 T cell anergy found in HIV-positive patients.