Viva-Natural, extracted from a dietary seaweed, containing a macrophage-activating polysaccharide, has been confirmed to be active against intraperitoneally implanted Lewis lung carcinoma (LLC) and spontaneous AKR T cell leukemia. The antitumor potential against LLC has been evaluated in comparison with standard synthetic immunomodulators such as pyran copolymer (MVE-2), isoprinosine, levamisole, and tilorone while manipulating the immune systems by immunosuppressive agents, cyclophosphamide (CY) and 2-chloroadenosine. The anti-LLC activity of Viva-Natural has been found to be superior to that of isoprinosine but inferior to that of MVE-2. LLC-enhancing effect of CY could be partially reserved by the subsequent administration of Viva-Natural or MVE-2 but not by isoprinosine. 2-Chloroadenosine, a specific macrophage inhibitor, abrogated the anti-LLC activity of Viva-Natural and isoprinosine but not the activity of MVE-2. Levamisole and tilorone showed no anti-LLC activity. Ethanol-precipitable fraction of water-soluble part of Viva-Natural (crude polysaccharide) demonstrated curative activity similar to that of MVE-2. Viva-Natural reversed the potentiation effect of ciclosporin on the development of leukemia in AKR mice at preleukemic stage.