Recently, a new class of human dendritic cell (DC) precursors has been described in the peripheral blood recognized by the mAb M-DC8. These cells represent∼ 1% of PBMC and acquire several characteristics of myeloid DC upon in vitro culture. In this report we show that M-DC8+ monocytes secrete in response to LPS> 10 times the amount of TNF-α as M-DC8− monocytes, but produce significantly less IL-10. Consistent with a role in inflammatory responses, we found that M-DC8+ cells localized in the T cell area of inflamed human tonsils and in the subepithelial dome region of Peyer’s patches. In patients with active Crohn’s disease, abundant M-DC8+ cells were detectable in inflamed ileal mucosa, which were entirely depleted after systemic steroid treatment. Our results indicate that M-DC8+ cells are cells of DC phenotype in inflamed mucosa-associated lymphoid tissue that may contribute to the high level of TNF-α production in Crohn’s disease. We infer that selective elimination of M-DC8+ cells in inflammatory diseases has therapeutic potential.