Effects of glucose on the catecholamine release from the hypothalamic fragments in vitro were studied. Basal release of catecholamines was inversely related to the concentrations (5 ~ 30 mM) of glucose in the incubation medium. Glucose did not affect the 30 mM K+-stimulated release of catecholamine. In the presence of tetrodotoxin (10μM), the inhibitory effect of glucose on the basal release of catecholamines was largely persisted, but the inhibitory effect of 30 mM glucose on dopamine release was largerly blocked. In the presence of both tetrodotoxin (10μM) and desipramine (3μM), glucose failed to affect the basal catecholamine release. The results suggest that glucose modulates the catecholamine release through a direct action on the catecholaminergic nerve terminals, as well as through a trans-synaptical action. The glucose-modulation of the catecholamine release may explain, at least in part, the diabetes-induced changes in the hypothalamic catecholamine metabolism.