We examined the response of plasma glucose concentration and glucose counterregulatory factors (eg, glucagon, epinephrine, growth hormone, cortisol, and norepinephrine) to insulin-induced hypoglycemia in four patients with Shy-Drager syndrome and in five control subjects to determine if glucose counterregulation occurred in the patients with sympathetic and parasympathetic nervous system defects. The recovery of plasma glucose from hypoglycemia in a slower phase in the patients appeared to be almost similar to that in the control subjects, along with the absence of an initial rapid recovery phase; that is, there was no significant difference in the plasma glucose levels observed at any point between the patients and the control subjects. Although the insulin-induced hypoglycemia in the control subjects provoked a rapid release of epinephrine, followed by an increase in the plasma glucagon, growth hormone, and cortisol levels, it did not cause a significant increase in any of the glucose counterregulatory factors in the patients. Our findings that the restoration of normoglycemia after insulin-induced hypoglycemia occurred despite no significant increase in the counterregulatory hormonal factors suggest that other glucose counterregulatory mechanisms (eg, increased glucose release from the liver by the intrinsic effect of hypoglycemia on the liver) than the hormonal glucose counterregulatory factors might play an important role in the recovery of plasma glucose from insulin-induced hypoglycemia in a state of chronic deficiency of hormonal factors.