(1-->3)-beta-D-Glucans remained in the liver and spleen for long time, i.e. more than a month, without major structural changes/because there is no specific metabolic pathway for it in the body. However, biological activities, such as priming activity to LPS, triggered TNF-alpha synthesis, and antitumor activity was reduced more quickly. In this paper, we demonstrated the contribution of protein binding in inactivating beta-glucans. A particle beta-glucan preparation, zymosan, was treated with serum or plasma at 37 degrees C and their various biological activities were compared with zymosan alone. Such biological activities as antitumor activity, TNF-production, IL-6 production, complement activation and vascular permeability were significantly decreased by serum or plasma treatment. These results strongly suggested that the binding of serum or plasma protein(s) to beta-glucans would be a key step in inactivating a particle beta-glucan in the body.