Dendritic cells (DC) are critically involved in the initiation of primary immune processes, including tumor rejection. In our study, we investigated the effect of interleukin-10 (IL-10)–treated human DC on the properties of CD8⁺ T cells that are known to be essential for the destruction of tumor cells. We show that IL-10–pretreatment of DC not only reduces their allostimulatory capacity, but also induces a state of alloantigen-specific anergy in both primed and naive (CD45RA⁺) CD8⁺ T cells. To investigate the influence of IL-10–treated DC on melanoma-associated antigen-specific T cells, we generated a tyrosinase-specific CD8⁺ T-cell line by several rounds of stimulation with the specific antigen. After coculture with IL-10–treated DC, restimulation of the T-cell line with untreated, antigen-pulsed DC demonstrated peptide-specific anergy in the tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells reversed the state of both alloantigen- or peptide-specific anergy. In contrast to optimally stimulated CD8⁺ T cells, anergic tyrosinase-specific CD8⁺ T cells, after coculture with peptide-pulsed IL-10–treated DC, failed to lyse an HLA-A2–positive and tyrosinase-expressing melanoma cell line. Thus, our data demonstrate that IL-10–treated DC induce an antigen-specific anergy in cytotoxic CD8⁺ T cells, a process that might be a mechanism of tumors to inhibit immune surveillance by converting DC into tolerogenic antigen-presenting cells.