The cellular location and carbohydrate specificities of a glycoprotein recognition system on rat hepatic sinusoidal cells have been determined. The hepatic receptors which recognize N-acetylglucosamine/mannose terminated glycoproteins are located predominantly on endothelial cells. These receptors are glucose sensitive. Fasting increases the number of these receptors whereas diabetes mellitus abolishes this effect of fasting and impairs the function of this receptor in vivo. These findings suggest a mechanism for abnormal glycoprotein metabolism in diabetes mellitus. This carbohydrate recognition system may play an important role in the removal of potentially autodestructive glycoprotein lysosomal hydrolases and other glycoprotein enzymes from the circulation under normal physiological conditions and in disease states.