Abstract The alterations in hepatic glucose and glycogen catabolism were evaluated in rats bearing the Walker-256 tumor. Food intake was monitored concomitantly with measurements of the in vivo hepatic glycogen levels. Glycogenolysis, glycolysis and oxygen uptake were measured in the isolated perfused liver. The hepatic glucose phosphorylating capacity was measured in the high-speed supernatant fraction of liver homogenates. Food intake was 21.4% reduced in tumor-bearing rats; the glycogen levels were decreased by 63.6%. Initial basal rates of glucose release (glycogenolysis) and lactate+pyruvate production from endogenous glycogen (glycolysis) in the perfused liver were not changed by the tumor-bearing state, resulting in a higher relative rate of glycogen breakdown (% of glycogen degradation per unit time). In absolute terms stimulation of glycogen mobilization by glucagon or norepinephrine was smaller in the tumor-bearing state. The percentage of extra glycogen degradation per unit time caused by both hormones, however, was practically the same in the control and in the tumor-bearing state. The hepatic glucose phosphorylating capacity was reduced from 3.92±0.39 nmol min −1 (mg protein) −1 in normal rats to 2.61±0.23 nmol min −1 (mg protein) −1 in livers from tumor-bearing rats. Glycolysis from exogenous glucose (20 mM) in perfused livers was diminished from 0.136±0.023 μmol min −1 (g liver) −1 in normal rats to 0.046±0.008 μmol min −1 (g liver) −1 in tumor-bearing rats. It can be concluded that livers from rats bearing the Walker-256 tumor are less able to transform glucose and accumulate glycogen while possessing a greater tendency of releasing glucose from the glycogen stores.