(1->3)-b -Glucans exhibit a variety of biological activities, and the significance of these activities is dependent on the structure of the -glucans, such as solubility in water, molecular weight, degree of branching, and conformation. We have been analyzing the relationship between structure and activity of "gel-forming, high-molecular weight, soluble -glucans," such as schizophyllan (SPG), SSG, OL-2, and grifolan (GRN). We have a tentative conclusion that the soluble -glucans have almost no toxicity and that some of the activities, such as NO synthesis, vascular permeability, inflammatory cytokine synthesis, and limulus factor G activation, are significantly dependent on the conformation (single helix) of the -glucans. In addition, only GRN produced significantly high concentration of TNF- from macrophages in vitro. However, we exceptionally found that all the -glucans tested showed lethal toxicity in mice when administered with indomethacin. Large number of mice died within a week from the -glucan administration. Cytokine concentrations in sera of these mice were significantly increased by this treatment, suggesting that the lethal toxicity might be related to aberrance of the cytokine network.