Metabolic degradation of a soluble highly branched (-->3)-beta-D-glucan, SSG, was examined in mice using a macrophage blocker, gadolinium chloride (GdCl3). Intraperitoneally administered SSG distributed in the liver was slowly degraded, and after 5 weeks about 30% of the SSG became anionic. In addition, it is suggested that the metabolites would contain fewer branching points as assessed by the reactivity to limulus factor G. On the other hand, in the spleen, the molecular weight and the degree of branching of SSG were not changed for at least 5 weeks. Blockade of Kupffer cells by GdCl3 did not significantly change the distribution ratio of SSG in the liver. However, the treatment significantly delayed the degradation of SSG. These results suggested that Kupffer cells play important roles, not in the distribution, but in the oxidative degradation of SSG in the liver. In addition, splenic macrophages did not significantly contribute to the metabolic degradation of SSG.