This study examined factors associated with the anorexia of chronic liver disease and obesity following liver transplantation. Sixty-seven patients with chronic liver disease and a group of 18 healthy volunteers were recruited. A sub-group of 23 patients who underwent liver transplantation were reviewed every three months on three occasions. Nutritional status was determined using body habitus measurements and multi-frequency impedance analysis. Indirect calorimetry was used to determine energy and substrate metabolism in the fasted and fed state. Basal and post-prandial insulin and glucose concentrations were measured. Diet diaries were used to estimate energy and macronutrient intake and macronutrient preference was identified using a single food varying in fat and carbohydrate content. Patients with cirrhosis of hepatocellular origin (alcoholic liver cirrhosis, cryptogenic cirrhosis) had the greatest disturbances in substrate metabolism, depressed dietary intakes and poorest nutritional status when compared with patients with biliary cirrhosis and control subjects. These findings suggest that aberrant metabolism may contribute to anorexia and impact on nutritional status in patients with hepatocellular cirrhosis. No differential effect was observed when patients were stratified for severity of disease. Following liver transplantation, patients weight exceeded pre-illness values by 7% and this increase in body weight was accounted for by fat mass but not lean tissue. A decrease in resting energy expenditure was observed and a 5% increase in the dietary intake of fat derived energy. No association between immunosuppressive medication and body weight was seen. Multiple regression analysis revealed that the strongest predictor of weight gain was resting energy expenditure. These findings suggest that the liver transplant procedure per se is implicated in the energy economy and fat hyperphagia observed following liver transplantation which may be a result of denervation and the loss of afferent input and efferent outflow.