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The autoimmune aetiology of type I diabetes has been well documented. We studied whether anti-insulin anaphylactic antibodies were present on the membrane of basophils from type I diabetics by the toluidine blue method (detecting basophil activation after stimulation by insulin). We observed that basophils of recently diagnosed insulin-dependent diabetic patients (n = 13) were statistically more frequently activated by insulin than basophils from nonin-sulin-dependent diabetics (p < 0.002, n = 8) or non-diabetic subjects (p < 0.05, n = 9). Basophils from normal donors were passively sensitized with plasma from insulin-dependent diabetics and could then be activated by insulin. This sensitization still occurred when using plasma previously heated to 56°C, indicating that the sensitizing antibodies were not of the IgE class. When basophils from type I diabetics were preincubated with anti-IgG subclasses, only anti-IgG4 monoclonal antibodies inhibited the insulin-induced basophil activation. By contrast, preincubation with blocking concentrations of anti-IgG1-3 antibodies or desensitization of the IgE pathway did not modify basophil activation. These experiments strongly suggest the presence of anti-insulin antibodies of the IgG4 subclass in insulin-dependent diabetics before any insulin administration and provide a simple tool to complement the usual method of detecting auto-antibodies in diabetes.