D-Glucose improves memory in animals and humans and in subjects with memory pathologies. To date, the accepted conclusion drawn from animal research is that D-glucose improves memory via alterations in central cholinergic systems. However, recent evidence suggests that a sugar which does not cross the blood-brain barrier also facilitates memory (Talley, Arankowsky-Sandoval, McCarty, & Gold, 1999). The present study examined the effects of peripherally administered L-glucose, a stereoisomer of D-glucose, in male mice. Intraperitoneal administration of L-glucose (300 mg/kg) before testing enhanced place learning in the Morris water maze. Mice injected with L-glucose had significantly shorter escape latencies than mice injected with saline (1 ml/kg). Effects were observed on both reference memory and working memory tasks. L-Glucose did not facilitate performance on either task when it was simultaneously administered with cholinergic antagonists that are excluded from the central nervous system. Thus, simultaneous administration of either methyl-scopolamine (0.3 mg/kg), a peripherally acting muscarinic receptor blocker, or hexamethonium (1 mg/kg), a peripherally acting nicotinic receptor blocker, reversed the effect of L-glucose on memory. These findings suggest that the memory effects of L-glucose may be mediated by facilitated acetylcholine synthesis and/or release in the peripheral nervous system.