It has been speculated that insulin antibodies may contribute to the hypoglycemic attacks in insulin-treated diabetic patients. To address this hypothesis, we analyzed in a first part of the study the frequency to hypoglycemia in two groups of diabetic patients, one (Group A, 38 cases) with at least two episodes of severe hypoglycemia in the last year and another (Group B, 38 cases) without severe hypoglycemia in the last 3 years. In the second part of this study, we analyzed the frequency of severe and moderate episodes of hypoglycemia in another two groups of diabetics, one (Group C, 32 cases) with high insulin antibody titre (greater than or equal to 20% binding, mean +/- SD 31.2 +/- 8.1%) and another with low insulin antibody titre (less than 10% binding, mean +/- SD, 5.1 +/- 2.2%). No significant difference was found for bound insulin between diabetics with frequent hypoglycemic episodes (2.3 +/- 0.2/patient/year--Group A) and those without severe hypoglycemic episodes (Group B), i.e., bound insulin 4.89 +/- 3.21% in group A versus 5.32 +/- 4.5% in group B. Conversely, the frequency of severe episodes of hypoglycemia was similar in diabetic patients with high (31.2 +/- 8% binding in group C) and respectively low (5.1 +/- 2.1% binding in group D) insulin antibody titre, i.e., 0.15 episodes/patient/year in group C and 0.17 episodes/patient/year in group D.