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Many polysaccharides obtained from natural sources are considered to be biological response modifiers and have been shown to enhance various immune responses. Here, we investigated the immunomodulating effects of arabinogalactan (AG) and fucoidan (FU) in vitro. Mouse spleen lymphocytes became cytotoxic to tumor cells after culture with AG and FU at concentrations of 10-100 microg/mL. Also, AG and FU were mitogenic in spleen lymphocytes and peripheral macrophages. Macrophages treated with AG and FU (10-100 microg/mL) exhibited induced tumoricidal activity and increased phagocytosis, lysosomal enzyme activity, and production of nitrite, H2O2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6. However, AG and FU had little effect on the level of IL-1beta. Thus, the tumoricidal effect of AG- and FU-activated macrophages appeared to be mainly mediated by production of free radicals (NO and H2O2) and cytokines (TNF-alpha and IL-6). These data suggest that AG and FU are activators of lymphocytes and macrophages. This property may contribute to their effectiveness in the immunoprevention of cancer.