In mice, the hyperglycemic response to a stress, such as repeated orbital puncture, evoked a hyperglycemia through activation of the adrenal medulla and consequent release of catecholamines. This hyperglycemia could be blocked by pretreatment of the mice with the ganglionic blocking agent, chlorisondamine. The hyperglycemic response evoked by single doses of serotonin receptor blocking agents, such as cyproheptadine and methysergide, or by dopamine receptor blockings drugs, such as haloperidol or chlorpromazine, could also be blocked by pretreatment with chlorisondamine. Administration of a single dose of the muscarinic agonist, oxotremorine, also resulted in a hyperglycemia that was blocked by chlorisondamine. The results are compatible with the hypothesis that the adrenal medulla is under the control of a central cholinergic pathway with dopaminergic and serotonergic modulating systems.