Human immunodeficiency virus (HIV-1) tat, a trans-activator of the HIV long terminal repeat, is essential for HIV replication and causes inhibition of antigen-mediated T cell proliferation. To understand the mechanism of inhibition of T cell proliferation, we have investigated the regulation of IL-2 production and its receptor expression on a human CD4+ T lymphoid cell line (H9) transfected with HIV-1 tat gene. When cells were activated by mitogens, as compared to control cells, a significant decrease in both IL-2 mRNA and protein was observed in tat-transfected cells. Similarly, mitogen-induced IL-2R alpha and IL-2R beta mRNA and surface expression of IL-2R alpha and IL-2R beta chains were also significantly decreased in tat-transfected cells compared to control cells. Only IL-2 receptor density was decreased; the affinity of the ligand for the receptor appeared to be unchanged. In contrast to our previous studies with B-lymphoblastoid cell line (Puri RK and Aggarwal BB: Cancer Res 1992; 52:3787-3790), IL-4R expression was unaltered by HIV tat transfection in the H9 T cell line, indicating a cell type-specific phenomenon. Owing to the central role of IL-2 immunoregulation, our data suggest that immunosuppressive effects of HIV-1 tat may be mediated at least in part through the inhibition of both IL-2 production and IL-2 receptor expression.