Protein and glycoprotein synthesis and secretion by isolated perfused livers and isolated hepatocytes from control and streptozotocin diabetic rats have been investigated. (3)H-Leucine and (14)C-glucosamine incorporation were used as markers for protein and glycoprotein synthesis and secretion. Total protein secretion was reduced by 50% in the perfusate (p < 0.001) and by 36% in hepatocytes (p < 0.05), but glycoprotein secretion was unchanged in both preparations from diabetic animals. These differences were not due to changes in the available pool sizes of the different labels. On liver fractionation, all membrane components from the liver of diabetic animals had lowered (3)H-leucine: (14)Cd-glucosamine ratios in relation to the control animals. This was caused by enhanced glucosamine incorporation in relation to that of leucine. It is suggested that whereas protein synthesis is decreased in acutely diabetic rats, the production of glycoproteins is normal and occurs by the same pathway as in control animals.