The interactions between ureogenesis and gluconeogenesis from lactate have been studied in vivo by measurements of arteriovenous differences across the digestive tract and the liver in rats adaptated to 5 and 13% casein (high carbohydrate HC) or 50 and 90% casein (high protein, HP) diets. In contrast to HC diets, glucose absorption in portal vein was very limited with the 50% casein diet. Lactate released by the digestive tract was highest with HC diets, although not proportional to absorbed glucose, and was markedly reduced when large amounts of alanine were produced by the intestine. Glucose was removed by the liver in rats on HC diets, but was released with HP diets and during fasting. Lactate was efficiently removed by the liver in fasted rats; in contrast, there was a net hepatic release of lactate in rats on HP diets, while alanine was extensively taken up, due to a dramatic increase of portal alanine and of its hepatic extraction. The impaired uptake of lactate when gluconeogenesis from alanine was very active was concomitant to an increased hepatic lactate/pyruvate ratio, but without lactate accumulation. This could be interpreted in relation with an increase of the cytosolic NADH/NAD ratio caused by the conversion of large amounts of aspartate into malate via the urea cycle steps.