Interleukin-10 (IL-10) was originally identified as a cytokine produced by mouse TH2 cells that inhibits interferon gamma production by TH1 cells. Recently, human IL-10 has been sequenced and found to have approximately 70% homology with the BCRF-1 open reading frame of Epstein-Barr virus. Similar to mouse IL-10, human IL-10 has been found to inhibit interferon ~ production by human T cells, a property shared by the protein encoded by BCRF-1. The purpose of our investigation was to assess a possible role for IL-10 and BCRF-1 in the control of EBV infection. In initial experiments we have demonstrated that both human IL-10 as well as BCRF-1 protein are potent inhibitors of mitogen-induced T cell proliferation. This inhibitory effect is associated with inhibited IL-2 production and is reversed by addition of exogenous IL-2 to the suppressed cultures. Confirming previous observations, we also found that IL-10 and BCRF-1 protein inhibit Interferon gamma production. This effect, however, appears to be independent of the growth inhibitory functions of IL-10 and BCRF-1. In a subsequent set of experiments, we have examined whether IL-10 inhibition of T cell growth occurs through a direct effect on T cells or rather occurs indirectly acting upon a different cell type. Using purified T cells and a tetanous toxoid-specific T cell clone activated by immobilized OKT3, we found that IL-10 can act directly on the T cell. This finding is novel because previous data on this subject have strongly suggested that IL-10 does not affect T cells directly but always through the monocyte. Use of IL-10 as a direct inhibitor of human T cells will provide a valuable system for future investigation of the molecular basis for inhibition by IL-10.