Diet and alcohol consumption are significant contributors to health and disease worldwide. Liver disease is a consequence of poor diet and alcohol consumption; however preclinical animal studies have not adequately considered the combined effect of poor diet and chronic alcohol intake into study design. Given the physiological cross talk between the liver and kidney and the occurrence of hepatorenal syndrome in alcoholics, we set out to determine how poor diet and chronic alcohol intake influence liver and kidney health in mice. All experiments were performed in accordance with protocols approved by the Liberty University IACUC and conform to the FASEB standards for the use of animals in research and education. 3-week old male C57Bl/6 mice were purchased from The Jackson Laboratory and acclimated to the new environment and chow diet for 1-week. Mice were then given ad libitum access to chow (18% protein), our novel Americanized diet (AD), or a commercially available “Western” diet (WD) (n=6). After 6 weeks, all mice began a chronic alcohol exposure of 10% ethanol solution given as the only source of water for 3 weeks. Body weight, food, and beverage intake were recorded weekly. Systolic blood pressure was determined using a non-invasive tail-cuff method and renal blood flow estimated using contrast-enhanced ultrasonography. Mice were then euthanized and blood and liver tissues collected. Blood was analyzed for circulating ALT activity and HDL, triglycerides, and glucose concentrations. All statistical analyses were performed using general linear models in SPSS with “Diet” as the independent variable. Diet had a significant effect on ethanol consumption (P