In view of the facts that ginseng has been shown to improve age-related memory deficits and beta-amyloid-related peptides have been suggested to play a significant role in memory degeneration in the elderly, the present study was carried out to examine the effect of various ginsenosides on beta-amyloid peptides-modulated acetylcholine (ACh) release, a key neurotransmitter in memory processing, from the hippocampal slices. Addition of beta-amyloid fragment(25 - 35) (0.01 - 1 microM) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner and about 40 % reduction in ACh outflow was observed when incubating with the highest concentration of an amyloid fragment (1 microM). Inclusion of the ginsenoside components Rb(1) (0.1 microM), but not Rg(1), caused a rightward shift of the concentration-response curve of beta-amyloid. The reversal of the beta-amyloid-inhibited ACh release by Rb(1) was not blocked by tetrodotoxin (1 microM) indicating that an interaction occurs at the cholinergic synapse. These results suggest that Rb(1) may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides.