The effects of Gypsophila saponin, sodium dodecylsulfate (SDS) and Triton X-100 on volume changes and fragility of red blood cells were compared to ginseng saponin to elucidate whether there are any difference in their action on membrane lipid. Cell volume was decreased to about 38% in 1M NaCl and increased to about 20% in 1/10M NaCl. Hematocrit value was decreased by Gypsophila saponin, SDS, and Triton X-100 which caused hemolysis in isotonic NaCl solution. These detergents also inhibited increase of cell volume and accelerated hemolysis in hypotonic solution. However, ginseng saponin did not influence to osmotic volume changes and hemolysis of red blood cells. These results suggest that the disruptive effect of plant saponin on membrane barriers induced by removing membrane lipid is different from their source and ginseng saponin has very low affinity to membrane lipid.