The mechanism of the antitumoral effect of levan was studied in the C57BL mice-Lewis lung carcinoma system. Modulation of host immune response and a direct inhibitory effect on tumor cells were found. Local treatment was more effective when begun early. It reduced tumor incidence without affecting the size of developing tumors. Systemic treatment was more effective when started late, inhibiting equally the tumor size in all mice. Macrophages are involved in local, lymphocytes possibly in systemic, inhibition. A direct effect on tumor cells was suggested by a decrease in oncogenicity, following preincubation with levan. Levan augments the antitumoral effect of cyclophosphamide in vivo and in vitro.