Autoantibodies to the insulin receptor have been demonstrated to antagonize the physiologic actions of insulin, most often resulting in hyperglycemia unresponsive to massive doses of insulin (type B insulin resistance). Patients with these anti-insulin receptor antibodies typically have a coexistent autoimmune disorder, most commonly systemic lupus erythematosus (SLE) or undifferentiated autoimmune syndromes. Attempting to determine the prevalence and significance of anti-insulin receptor antibodies, sera from consecutive patients with SLE and early undifferentiated connective tissue disease (UCTD) were tested for the presence of anti-insulin receptor antibodies by radio-immuno assay. Thirty-eight patients participated in the study. Twenty-six had SLE and 12 had UCTD. One patient with SLE (2.6%) was positive for anti-insulin receptor antibodies. None of the patients demonstrated evidence of insulin resistance, hypoglycemia, ovarian hyperandrogenism, or acanthosis nigricans, findings commonly linked with the presence of anti-insulin receptor antibodies.The results presented here indicate that the incidence of anti-insulin receptor antibodies in patients with SLE or UCTD, without associated history of altered glucose metabolism, is quite low. Because in most cases the disturbance of glucose metabolism dominates the clinical picture at presentation and the associated systemic autoimmune syndrome presents either simultaneously with or subsequent to the diagnosis of diabetes, the measurement of anti-insulin receptor antibodies should be reserved for patients with indications of disordered glucose homeostasis.