IL-10 has previously been shown to inhibit cytokine production by Th1 cells by blocking macrophage accessory cell function. In this study we demonstrate that dendritic cell-induced Th1 proliferation was unaffected by IL-10, whereas macrophage-stimulated proliferation was inhibited in the same system. In contrast dendritic cell induced IFN-gamma production by the Th1 clones was down-regulated by IL-10. Inasmuch as dendritic cells have been shown to be potent APC for T cells in primary responses we determined the effect of IL-10 on dendritic cell-induced proliferation and IFN-gamma production by CD4+ and CD8+ T cells. Dendritic cells were effective at stimulating both proliferation and IFN-gamma secretion of CD4+ or CD8+ T cells in a primary allogeneic mixed leukocyte response. In contrast, IL-10 markedly inhibited dendritic cell driven IFN-gamma production by purified CD4+ and CD8+ T cells. Down-regulation of dendritic cell-induced IFN-gamma production suggests a role for IL-10 in inhibiting the initiation of cell-mediated immune responses.