Physiologic cell death via apoptosis occurs without inflammation or autoimmunity. Here, we investigated the outcome of the interaction of apoptotic cells with dendritic cells (DCs), which are potent professional APCs. DCs internalized apoptotic cells and processed them for presentation to both MHC class I- and class II-restricted T cells with an efficiency that was dependent upon the number of apoptotic cells. The latter event was accompanied by the autocrine/paracrine secretion of IL-1beta and TNF-alpha, with eventual DC maturation. High numbers of apoptotic cells, mimicking a failure of their in vivo clearance, are therefore sufficient to trigger DC maturation and the presentation of intracellular Ags from apoptotic cells, even in the absence of exogenous "danger" signals.