An attempt is made to review the steps in the biosynthesis of plasma proteins by the liver and to point out intermediate precursor forms that might escape to the plasma. With the use of immunochemical techniques such as immunofixation electrophoresis it is possible to identify these precursors when they present an unusual bands on protein electrophoresis. The discovery of the role of vitamin K in the formation of the blood-clotting proteins, for example, followed the immunochemical detection of an abnormal form of inactive prothrombin in plasma. The chief types of precursors likely to occur in blood are forms that are incompletely glycosylated, phosphorylated, or sulfated, or which are single peptide chains of multichain proteins. Precursors containing basic propeptides such as proinsulin or proalbumin may also appear. By being alert to the possible appearance of intracellular forms in plasma, the clinical chemist may be able to relate their presence to the nature of the disease process responsible.