Proinsulin-like components (proinsulin and its intermediate forms, PLC) and C-peptide have been identified as secretory products of the pancreatic beta cells in addition to insulin. Because a specific human proinsulin antiserum is not yet available, serum PLC can be measured with an insulin or C-peptide antiserum and a human proinsulin standard after separation of insulin and C-peptide by gel filtration. Assay of unextracted serum with these two immunoassay systems measures total insulin immunoreactivity (insulin + PLC) and C-peptide immunoreactivity (C-peptide + PLC), respectively. Fasting PLC in normal subjects ranged between 0.05 and 0.4 ng./ml. After oral glucose, PLC levels rose more slowly than insulin and peaked at a later time. In relation to insulin, the percentage PLC was high in the basal state and two to four hours after glucose. The serum PLC concentration has also been measured in a variety of disease states including obesity, acromegaly, myotonic dystrophy, uremia, myxedema and Cushing's syndrome. However, the most frequent and marked abnormality in its level has been found in patients with islet cell tumors. Equimolar amounts of C-peptide and insulin were found in serum of subjects with a wide range of insulin values. Thus the C-peptide level can be used as an indicator of beta cell secretory function. This application is especially useful in diabetic patients who develop circulating insulin antibodies in response to exogenous bovine or porcine insulin therapy. Measurement of serum C-peptide and proinsulin in these subjects has shown varying degrees of beta cell failure as well as marked fluctuations in secretory capacity in individual patients with progression of their disease. Preliminary results have indicated the immunological heterogeneity of other circulating peptide hormones and have shown that they may be synthesized and stored in a form different from the secreted molecule. The discovery of proinsulin has thus opened up new and exciting areas which may have wide application in endocrinology.