Dendritic cells (DCs) communicate with nonadaptive and adaptive lymphocytes on multiple levels. Efficient DC-lymphocyte interactions require that lymphocytes remain viable and functional also under conditions of oxidative stress, such as in microbial infection or in the malignant microenvironment. For this study, we exposed human T and NK cells to oxidants delivered either by autologous phagocytes or in the form of exogenous hydrogen peroxide. In accordance with earlier studies, these lymphocytes became dysfunctional and subsequently apoptotic. The presence of myeloid DCs efficiently rescued T cells (CD4+ and CD8+) and NK cells from oxidant-induced inactivation and apoptosis. The mechanism of the myeloid DC-mediated lymphocyte protection was, at least in part, explained by the capacity of the myeloid DCs to neutralize extracellular oxygen radicals, which, in turn, was reversible upon coincubation with a catalase inhibitor. Our results are suggestive of a novel aspect of DC-lymphocyte interaction that may have implications for lymphocyte function in inflamed tissue.