The present study tests the effects of glucose and choline, the biosynthetic precursors of acetylcholine, on passive avoidance behaviour and hippocampal acetylcholine release measured by microdialysis in awake mice. Glucose (10 and 30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately after training, dose-dependently enhanced retention in an inhibitory avoidance task. Combinations of low doses of glucose (10mg/kg) and choline chloride (20mg/kg) which alone were submaximally effective significantly increased retention latencies in a synergistic manner, an effect which was sensitive to atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose or choline were combined. Basal hippocampal acetylcholine release in mice habituated to their environment was not affected by administration of glucose and choline. However, when hippocampal acetylcholine release was stimulated either by infusion of scopolamine (0.3microM) or by transferring the mice into a novel environment, the combination of glucose plus choline further increased acetylcholine release to a significant extent. We conclude that low doses of glucose and choline act synergistically to improve memory storage, an effect which is due to facilitation of acetylcholine release. This finding reinforces the view that central cholinergic functions are influenced under certain conditions by dietary intake of precursors.