ABSTRACT In most diabetic patients treatment with commercial insulin preparations containing 1 to 2 per cent proinsulin, results primarily in the formation of antibodies reacting with both insulin and proinsulin. Later on the formation of antibodies reacting specifically with proinsulin also seems to occur. In some plasma samples from patients treated with porcine insulin it has been possible to demonstrate the formation of antibodies reacting with proinsulin and intermediate forms, but not with monocomponent insulin, dimer forms or C-peptide from porcine insulin. No reaction of bovine proinsulin with antibodies to porcine proinsulin could be demonstrated. The observations indicate that proinsulin has considerable significance for antibody formation in diabetic patients treated with the commonly available insulin preparations.