Dendritic cells (DCs) are a group of APCs that have an extraordinary capacity to interact with T and B cells and modulate their responses to invading pathogens. Although a number of defects in the immune system have been identified in sepsis, few studies have examined the effect of sepsis on DCs, which is the purpose of this study. In addition, this study investigated the effect of sepsis on macrophages, which are reported to undergo apoptosis, and MHC II expression, which has been noted to be decreased in sepsis. Spleens from 26 septic patients and 20 trauma patients were evaluated by immunohistochemical staining. Although sepsis did not decrease the number of macrophages, sepsis did cause a dramatic reduction in the percentage area of spleen occupied by FDCs, ie, 2.9±0.4 vs 0.7±0.2% in trauma and septic patients, respectively. The number of MHC II-expressing cells, including interdigitating DCs, was decreased in septic, compared with trauma, patients. However, sepsis did not appear to induce a loss of MHC II expression in those B cells, macrophages, or DCs that were still present. The dramatic loss of DCs in sepsis may significantly impair B and T cell function and contribute to the immune suppression that is a hallmark of the disorder.