In myotonic dystrophy, there is resistance of forearm muscle to physiologic concentrations of insulin. To determine whether this resistance is due to a shift in the dose-response curve resulting from decreased numbers of insulin receptors, we measured the effects of supraphysiologic insulinization (200 μU per kilogram per minute) on the uptake of glucose by forearm muscle in three patients with myotonic dystrophy and five denervated patients with comparable wasting. Although insulin levels were higher in patients with myotonic dystrophy than in controls, peak glucose uptake remained significantly lower in myotonic dystrophy patients. The findings are consistent with a postinsulin receptor defect of muscle and with altered membrane function in myotonic dystrophy.