We have evaluated the use of the immunosuppressant mycophenolate mofetil (MMF) in the treatment of severe insulin resistance caused by neutralising anti-insulin antibodies in type 1 diabetes mellitus (T1DM). A 12-yr-old boy with a 5-month history of T1DM developed severe immunological insulin resistance secondary to human insulin antibodies. Various different treatment modalities, including lispro insulin, intravenous insulin, prednisolone and immunoabsorption, were tried, all without a sustained response to treatment. Although the introduction of the immunosuppressant MMF only resulted in a small reduction in haemoglobin A1c (from 10.9 to 9.8%), it did result in a significant reduction in insulin requirements from 6000 to 250 U/d (75 to 3.1 U/kg/d), disappearance of the severe nocturnal hypoglycaemia associated with high titres of insulin antibodies and a reduction in the level of these antibodies from 34.6 to 2.7 mg/dL. MMF may be considered as a means of immunosuppression in patients with markedly raised insulin antibodies whose diabetes cannot be controlled with insulin alone.