Insulin withdrawal studies were performed in 12 Type 1 (insulin-dependent) C-peptide negative diabetic patients with low to moderate insulin antibody levels, to assess the biological availability of antibody-bound insulin and its clinical significance. There was a highly significant correlation between the extent to which the free insulin concentration was maintained during the period of insulin withdrawal and both the level of insulin-binding by serum and the total insulin concentration at the start of the study. During insulin withdrawal, the patients who best maintained their circulating free insulin levels showed the smallest increases in blood glucose and 3-hydroxybutyrate concentrations. We conclude that antibody-bound insulin is available for physiological action, and that in those individuals with moderate antibody concentrations it is capable, in the fasting state, of maintaining free insulin levels. In these circumstances insulin antibodies are behaving as simple carrier proteins.