The effects of ginseng total saponins (GTS) on L-glutamate-induced swelling of cultured astrocytes from rat brain were studied. Following exposure to 0.5 mM glutamate for 1 h, the intracellular water space (as measured by [3H]O-methyl-D-glucose uptake) of astrocytes increased three-fold with a morphological change: the disappearance of cellular processes. Simultaneous addition of GTS with glutamate reduced the astrocytic swelling in a dose-dependent manner. GTS at 0.5 mg/ml did not affect the viability of astrocytes for up to 18 h, which was determined by a colorimetric assay for cellular growth and survival. These data suggest that GTS prevents the cell swelling of astrocytes induced by glutamate.