To identify environmental stimuli that induce dendritic cell (DC) maturation, we exposed human monocyte-derived immature DC to apoptotic or necrotic cells and measured the levels of expression of costimulatory molecules and cytokine production. While most necrotic or apoptotic cells did not have any effect, some induced DC maturation as detected by up-regulation of CD83 and B7.2 and production of IL-12 and IL-6. The capacity of these cell lines to induce DC maturation was due to their contamination by mycoplasma, since the maturation-inducing effect disappeared when the cells were treated with cyproxin. Furthermore, cell lines deliberately infected with mycoplasma containing supernatant acquired the capacity to induce DC maturation. Our results reveal that DC are able to sense mycoplasma infection and mature as they do in response to most viruses and bacteria. In contrast, apoptotic or necrotic cells fail to induce DC maturation.