1. Livers from rats fed on a standard diet were perfused with whole blood, and infused continuously with glucose and fructose at equimolar rates.2. Infusion of fructose increased both the secretion of very-low-density-lipoprotein (VLDL)-triglycerides and the incorporation of free fatty acids (FFA) from the perfusate into VLDL-lipids, but neither of these two processes was affected by infusion of glucose.3. Infusion of fructose decreased the oxidation and increased the esterification of FFA, but glucose infusion had no effect on these processes. When fructose and glucose were infused together there was a further decrease in oxidation.4. When fructose was infused alone or together with glucose, blood concentrations rapidly became stabilized at those found in the hepatic portal vein in vivo, with similar rates of hepatic uptake to those found in the intact animal. Infusion of glucose alone resulted in continuously increasing perfusate glucose concentrations, and rates of uptake which were only 20 % of those for fructose. Blood glucose concentrations were reduced, and lactate concentrations were increased by fructose infusion, and when glucose and fructose were infused together there was a greatly increased rate of glucose uptake.5. Liver glycogen was not affected by the infusion of fructose or glucose alone; however, their combined addition significantly increased its concentration.6. Uptake of perfusate FFA was not affected by either fructose or glucose infusions.7. The results are discussed in terms of the differences in nutrition and metabolism between glucose and fructose, with particular reference to the development of hyper- triglyceridaemia.