THE effects of huperzine A on memory impairments induced by scopolamine were evaluted using a radial maze task and inhibition of cholinesterase in vitro compared with the effects of E2020 and tacrine. Scopolamine (0.2 mg kg−1) significantly impaired spatial memory in rats. Huperzine A (0.1–0.4 mg kg−1, p.o.), E2020 (0.5–1.0 mg kg−1, p.o.) and tacrine (1.0–2.0 mg kg−1, p.o) could reverse these scopolamine-induced memory deficits. The ratios of huperzine A, E2020 and tacrine for butyrylcholinesterase:acetylcholinesterase determined by a colourimetric method were 884.57, 489.05, and 0.80, respectively. The results demonstrated that huperzine A was the most selective acetylcholinterase inhibitor, and improved the working memory deficit induced by scopolamine significantly better than did E2020 or tacrine, suggesting it may be a promising agent for clinical therapy of cognitive impairment in patients with Alzheimer's Disease.