Twenty-two newly diagnosed insulin-dependent diabetics and 46 control subjects have been examined for Coxsackie B1-6 serum antibodies. Evidence for CoxB4 neutralizing antibodies at titers greater than or equal to 16 and two seroconversions for this single virus type were shown in the diabetic group (31.8% of patients with titers greater than or equal to 16 in comparison with 10% of controls, p = 0.08). Reduced titers against CoxB2 and CoxB5 in diabetics were also observed. In agreement with the majority of publications, these data suggest the hypothesis that CoxB4 infections are frequently associated with type 1 diabetes, and the positive relationship found only for this type of virus may be related to greater tropism for the pancreas. The specificity of this viral infection, as shown by our serologic results, could suggest a possible causative role in the development of type 1 diabetes only in a limited number of cases. The authors propose new studies with monoclonal and IgM specific antibodies, obtained from new isolates, to detect more accurately the qualiquantitative differences between type 1 diabetics and controls.