Excessive alcohol consumption represents a major human health threat. The frequency and severity of infections in alcoholics is often pronounced, suggesting impaired immune function in these patients. The precise effect of ethanol on cells of the immune system is poorly understood. We have previously shown that synthetic copolymers of L‐amino acids, GT and GAT, are powerful tools for clarifying the role of regulatory T‐cells in both cell‐mediated and humoral immunity in inbred mouse strains. We asked whether these same antigens would have application to a murine model of ethanol consumption. In this study, female mice were placed on a nutritionally complete liquid diet containing 35% ethanol‐derived calories. As control, mice either were placed on a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a solid diet consisting of standard laboratory chow and water ad libitum. Our data show that the liquid ethanol diet severely inhibits two measures of cell‐mediated immunity, the ability of responder B6 mice to make an anti‐GAT delayed hypersensitivity and GAT‐specific T‐cell proliferative responses as compared with pair‐fed liquid control diet or solid diet controls. On the contrary, this liquid ethanol diet does not significantly impair humoral immunity; it allows nonresponder C57BL/6 or C3H/HeN mice to respond in vivo to GT immunization. These findings suggested to us that the effect of ethanol may occur prior to antigenic stimulation, and this was confirmed by in v