Many polysaccharides isolated from plants are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. Here, we demonstrate that polysaccharide isolated from the radix of Platycodon grandiflorum (PG) has a unique mode of immunostimulation with regard to its cell-type specificity. PG was found to markedly increase polyclonal IgM antibody production and the proliferation of B cells, and to activate iNOS transcription and NO production in macrophages. Moreover, the intraperitoneal administration of PG in mice resulted in increased IgM antibody production in B cells, which were immunized by using T-dependent antigen sheep red blood cells (sRBCs). However, PG did not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the IL-4 expression of Th2 cells. Although PG and lipopolysaccharide (LPS) had a similar mode of action in B cells and macrophages, they were differentiated by the fact that PG-induced cellular activation was not inhibited by polymyxin B, a specific inhibitor of LPS. Anti-CD19 or anti-CD79b antibody blocked B cell proliferation and anti-CD14 or anti-CD 11b antibody decreased macrophage NO production, indicating the possible cellular binding sites of PG. Our results demonstrate that PG is a specific activator of B cells and macrophages but not of T cells, and suggest that PG is quite distinct from other well-known immunostimulants, such as lentinan and schizophyllan, which mainly act upon macrophages and T cells.