Although Kupffer cell, splenic, and peritoneal macrophage functions are markedly altered following trauma-hemorrhage (T-H), it remains unclear whether T-H also affects splenic dendritic cell (sDC) functions. We hypothesized that sDC functions will also be compromised following T-H. Male C3H/HeN (6- to 8-wk) mice were randomly assigned to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (four times the shed blood volume in the form of Ringer's lactate). Two hours later, the mice were sacrificed; sDC were isolated; and the changes in their apoptosis, MHC class II expression, and ability to produce costimulatory cytokines and Ag presentation were measured. The results indicate that sDC Ag presentation capacity was significantly decreased and MHC class II expression was also significantly decreased following T-H. Moreover, LPS-induced IL-12 production and LPS- or IL-12-induced IFN-γ production following T-H were significantly decreased. Thus, the markedly decreased M-H class II expression and cytokine (IL-12, IFN-γ) production following T-H may be the cause for the depressed sDC Ag presentation under those conditions. This depression in Ag presentation could contribute to the host's enhanced susceptibility to sepsis following T-H. Copyright © 2006 by The American Association of Immunologists, Inc.