Summary o 1. The livers of eight fasting dogs were perfused with oxygenated homologous blood in an isolated perfusion chamber to determine whether insulin altered the hepatic utilization of glucose. 2. No significant effect of insulin on hepatic glucose utilization was noted. 3. Factors that affect previous experiments are discussed and emphasis is placed upon utilizing a preparation totally free from interfering feedback stimuli. 4. A short discussion is given relating to the actual site of insulin activity in light of these paradoxical findings.