A 60-year old male diabetic patient treated with insulin for 6 years developed ketosis whenever an attempt was made to replace porcine insulin by mixed bovine and porcine insulin. That this resistance was specific to bovine insulin and of immune origin was demonstrated by in vivo and in vitro studies. The in vivo study used a Biostator artificial pancreas: rapid decrease of plasma glucose concentrations was observed under insulin infusion at a constant rate of 200 mU/min with either porcine or semi-synthetic human insulin despite maximum glucose infusion rate (400 mg/min), but not with bovine insulin and a low glucose infusion rate (150 mg/min). In the in vitro study, high levels of anti-insulin antibodies (11.4 m U/ml, Christiansen method) were found in the plasma, and the curves of competitive binding of radiolabelled insulin to the patient's IgG in the presence of unlabelled porcine or bovine insulin showed a 50% decrease of total binding with 0.12 ng/ml of bovine insulin and 25 ng/ml of porcine insulin, suggesting that the affinity of these antibodies for the former was 200 times higher than for the latter.