Acute alcohol administration has minimal effects on basal immune function. However, when the immune system is challenged, acute alcohol administration alters the immune system's response. In the first 3 h after infection or traumatic injury, the presence of alcohol is associated with a decreased inflammatory response. This defect lasts long after the alcohol is cleared. Conversely, by 48 h after traumatic injury, the presence of alcohol is associated with a heightened inflammatory response. Aside from its in vivo actions, systemic administration of alcohol also alters the ex vivo response of immune cells, resulting in a decreased production of multiple cytokines after stimulation by lipopolysaccharide, concanavilin A, zymosan, and CpG DNA. Here, we describe a standardized model of acute administration of ethanol to mice used to study both the in vivo and ex vivo responses of immune cells to ethanol.