Assessment of beta-cell function in insulin-treated diabetes is hampered by the presence of circulating insulin antibodies, which interfere with the commonly used insulin immunoassay. The development of an immunoassay for C-peptide has enabled beta-cell secretory products, in addition to insulin, to be monitored in the circulation of such patients. Using this assay, we studied the progressive changes in beta-cell secretion in three insulin-treated diabetic patients with hyperglycemia and ketonemia. Serum C-peptide immunoreactivity increased during the remission phase of the diabetic state, suggesting that the improvement in carbohydrate tolerance was due to renewed beta-cell secretion. Eventual clinical relapse was associated with decreasing serum C-peptide immunoreactivity. These results confirm the long held clinical impression that the cause of the remission phase in diabetes is usually resumption of beta-cell secretory activity. (N Engl J Med 288:1144–1148, 1973)