1 Intravenous injection of 2-deoxy-glucose (3 mmol/kg) increases plasma levels of insulin and glucose in the mouse. This study investigated the contribution of various autonomic receptors to the plasma insulin response. 2 Pretreatment with the cholinergic antagonist methylatropine abolished the response completely. 3 Pretreatment with the alpha-adrenoceptor antagonist phentolamine caused a potentiated response, whereas the beta-adrenoceptor antagonist L-propranolol had no effect. 4 Pretreatment with methylatropine and phentolamine combined caused a small insulin response, which was inhibited by propranolol. 5 Pretreatment with the nicotonic antagonist hexamethonium abolished the response. 6 It is concluded that 2-deoxy-glucose induces a stimulation of insulin secretion in vivo in the mouse predominantly by a cholinergic mechanism. 7 2-Deoxy-glucose also activates alpha-adrenergic mechanisms which affect the size of the insulin secretory response. beta-Adrenoceptor and non-adrenergic, non-cholinergic mechanisms seem to be less important.