The significance of insulin antibodies in determining diabetic control was examined in 56 patients treated with insulin. Diurnal changes in blood glucose, serum free insulin and bound insulin concentrations were measured. C-peptide concentrations before and after meals were measured as an index of residual insulin secretion. The control of blood glucose was estimated by the calculation of M-value (Schrichtkrull). The SD/mean of serum free insulin in patients with high insulin antibody titers was significantly lowered. This finding suggests that insulin antibodies have a buffer action of stabilization of serum free insulin. The buffer action of the insulin antibodies was affected by quantitative changes of bound insulin concentrations, which were accompanied by concomitant changes in free insulin concentrations within physiological limits. The capacity of the buffer action of insulin antibodies seems to be determined not only by the titer of insulin antibodies, but also by quantitative changes in free and bound insulin concentrations. In patients with antibodies of high buffer action, diurnal blood glucose levels were stable. Insulin antibodies seem to have a stabilizing action of blood glucose levels. Thus, insulin antibodies are thought to be an important factor in the control of blood glucose. In insulin-treated diabetics, serum free insulin levels in patients with obesity or liver dysfunction were as high as in non-insulin treated diabetics with these disorders.