Mechanisms for the development of cancer cachexia are not well defined. Oxygen consumption and the capacity of the host liver to metabolize lactate were studied in isolated hepatocytes from sarcoma-bearing rats (TIH) and pair-fed controls (CH). Basal oxygen consumption (without exogenous substrate) is significantly increased by 65% in the TIH as compared to the CH. The addition of a physiologic concentration of lactate stimulated oxygen consumption over the already stimulated basal state by 13% in the TIH compared to 5% in the CH. When the hepatocytes are incubated with 1.5 mM of [U-14C]lactate, glucose production, lactate oxidation, and entry of lactate carbons into nonsecretory protein are significantly increased in the TIH. Associated with this stimulation is a significant decrease in lactate incorporation into glycogen and lipid in the TIH. This study suggests that the tumor-influenced liver utilizes lactate at an increased rate and its intermediary metabolism is directed toward energy utilization rather than energy storage. The enhanced metabolic processes in the tumor-influenced liver are associated with an increased oxygen consumption which may be a contributory factor to the negative energy balance, a characteristic of cancer cachexia.