BACKGROUND/AIMS: The liver is regarded the most important source of glucose production and it is common practice to administer glucose during human liver transplantations to avoid hypoglycaemia. The purpose of this study was to evaluate the importance of extra-hepatic contribution (kidney, gut and muscle) to the glucose homeostasis in the anhepatic pig and in man during the anhepatic phase of human liver transplantations. METHODS: Blood glucose and lactate were monitored in the anhepatic phase in 46 patients undergoing liver transplantation. Arterial-venous differences of lactate, glucose, glycerol, alanine and free fatty acids were measured over kidney, gut and hind leg in 18 pigs made anhepatic. RESULTS: Blood glucose did not change significantly and blood lactate increased only marginally during the anhepatic phase of human orthotopic liver transplantation. In the anhepatic pig, however, blood glucose decreased with a halflife of about 26 min and blood lactate increased. Kidney gluconeogenesis was 0.116+/-0.016 mmol min(-1). Fifty percent of kidney glucose output could be accounted for by lactate- and glycerol uptake. CONCLUSIONS: The results show that in humans extra hepatic gluconeogenesis is sufficient to maintain normal blood glucose in the anhepatic phase of orthotopic liver transplantation, while in the pig this was not the case.