Alternative medicines such as herbal products are increasingly being used for preventive and therapeutic pur-poses. Ginseng is the best known and most popular herbal medicine used worldwide. In spite of some beneficial effects of ginseng on the nervous system, little scientific evidence shows at the cellular level. In the present study, I have examined the direct modulation of ginseng total saponins and individual ginsenosides on the activation of Ca^(2+) channels and NMDA-gated channels in cultured rat dorsal root ganglion (DRG) and hippocampal neurons, respectively. In DRG neu-rons, application of ginseng total saponins suppressed high-voltage-activated Ca^(2+) channel currents and ginsenoside Rg₃, among the 11 ginsenosides tested, produced the strongest inhibition on Ca^(2+) channel currents. Occlusion experiments using selective Ca^(2+) channel blockers revealed that girisenoside Rg₃could modulate L-, N-, and P/Q-type currents. In addition, ginsenoside Rg₃also proved to be an active component of ginseng actins on NMDA receptors in cultured hip-pocampal neurons. Application of ginsenoside Rg₃suppressed NMDA-induced［Ca^(2+)］_(i) increase and -gated channels using fura-2-based digital imaging and patch-clamp techniques, respectively. These results suggest that the modulation of Ca^(2+) channels and NMDA receptors by ginsenoside Rg₃could be part of the pharmacological basis of ginseng actions in the peripheral and central nervous systems.