Background: Antiviral cellular immune responses may influence immunological homeostasis in HIV-infected persons. Recent data indicate that Vγ9/Vδ2 T lymphocytes display potent cytotoxic activities against human cells infected with certain viruses including HIV. Understanding the role of γδ T cells in the course of HIV infection may be helpful for designing novel treatment strategies for HIV-associated disorders. Materials and Methods: The constitutive recognition of Daudi cells and monoethyl pyrophosphate (Etpp) by peripheral blood Vγ9/Vδ2 T cells was assessed using a proliferation assay. The cytotoxicity of Daudi-stimulated lymphocyte populations was measured by chromium release assays. The HIV infectivity for γδ T cell clones was determined by measuring the levels of HIV p24 in cell supernatants. The effect of in vitro HIV-infection on cytokine mRNA production by γδ T cell clones was assessed by PCR. Results: The constitutive proliferative responses of peripheral blood Vγ9/Vδ2 T cells and the lytic functions of Daudi-expanded lymphoid cells from HIV+ persons were substantially diminished in comparison with those of HIV-seronegative persons. These alterations were present in asymptomatic HIV+ persons prior to substantial αβ CD4+ T cell loss. Productive HIV infection of γδ T cells in vitro had no measurable effect either on their proliferative response to Daudi stimuli or on the expression of cytokine mRNAs for IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-13. Conclusions: The constitutive responsiveness of Vγ9/Vδ2 T lymphocytes to Daudi and Etpp is severely altered in HIV+ persons. HIV infection of γδ T cells in vitro does not substantially change their cytokine expression or antigenic response.