Recent studies indicate that C‐peptide, when given to patients with insulin‐dependent (Type 1) diabetes mellitus (IDDM), exerts significant effects on microvascular and neuronal functions. Adjuvant therapy with C‐peptide has been advocated in the treatment of IDDM patients. Since endogenous insulin secretion is believed to be of importance for the alpha‐cell function, we addressed the issue whether C‐peptide given acutely interferes with the responses to hypoglycaemia. Seven IDDM patients were randomly exposed to hypoglycaemia with and without exogenous C‐peptide. Insulin and and C‐peptide were given intravenously in equimolar amounts for 3 hours. The decrease of blood glucose was faster and more pronounced during C‐peptide infusion, yielding a significantly lower AUC 0–180 min of blood glucose (38.5 ± 1.6 vs 44.4 ± 2.2 mmol l⁻¹ h⁻¹ ; p  = 0.032). No difference between the two experiments was found concerning glucagon when the AUC, Δ‐values or levels at separate points of time were calculated. In conclusion, the main finding of this study was that exogenous C‐peptide, given acutely, gave rise to a more rapid onset of hypoglycaemia yielding no detectable differences with respect to the response of glucagon and other counterregulatory hormones. © 1997 by John Wiley & Sons, Ltd.