The immune response to trauma, shock, and/or sepsis appears to exhibit a bimodal response, in which there is an early exaggerated inflammatory response, giving way over time to a state of hyporesponsiveness or immune dysfunction. This state of immune dysfunction is frequently associated with increased infectious complications and/or mortality, seen following shock or trauma. In this article, we present an overview of some of those changes that have been seen with respect to the process of major histocompatibility class II (MHC class II) antigen presentation by macrophage, a key component of the overall host immune response to foreign bacterial and/or fungal pathogens encountered following shock/trauma (with a particular emphasis on hemorrhagic shock as a component of traumatic shock). With respect to the overall process of antigen presentation, defects (dysfunction) are evident not only in models of shock and sepsis, but also in traumatized patients. Studies of the capacity of a monocyte's/macrophage's ability to present antigen indicate that defects can be detected, not only in those steps involved in antigenic processing, but also in MHC class II molecule expression and accessory molecule function (or its inhibition) following shock. Those changes in the macrophage's capacity to process antigen seen during the first 24 h after hemorrhagic shock appear to be associated with the cell's metabolic response to regional hypoxia and/or the shift to proinflammatory mediator release (tumor necrosis factor, interleukin [IL]-1, IL-6, etc.). This initial acute response to shock appears to act as the nidus for chronic anti-inflammatory mediator release (prostaglandin E2, transforming growth factor-beta, IL-10, IL-4, nitric oxide, etc.), which may mediate the sustained depression of the antigen-presenting cell's function.