Peripheral glucose administration attenuates impairments produced by peripheral injections of the opioid agonist, morphine, on spontaneous alternation. Injections of opioid agonists directly into the medial septum also impair memory. The present experiments examined whether systemic and intraseptal glucose injections could attenuate deficits on spontaneous alternation and inhibitory avoidance in rats treated with intraseptal morphine. Morphine (3.95 nmol) injected into the medial septum significantly impaired performance on spontaneous alternation and inhibitory avoidance tasks. Both systemic (100 mg/kg, i.p.) and intraseptal (18.33 nmol) injections of glucose, administered concomitantly with intraseptal morphine, attenuated the morphine-induced impairments on these tasks in rats. These findings suggest that one brain region where glucose may act is the medial septum, possibly by releasing opioid inhibition of cholinergic activity.