Serum IgG subclass antibodies to insulin were semiquantitatively estimated using a highly sensitive and specific technique of enzyme-linked immunosorbent assay. The three groups of patients (categorised on the basis of duration and dose of exogenous insulin administered) showed a variable pattern. In spite of considerable variations from patient to patient in a group, IgG1 and IgG2 levels were higher in patients receiving a low dose of insulin for 9–18 and 30–72 months, respectively, while in the patients on high dose of therapeutic insulin, IgG4 well predominated over all other subclasses. It is postulated that IgG4 antibodies are directed against the biologically active site of insulin and explains the high requirement of insulin in these patients.