Summary Serum obtained from mice 3 to 5 weeks after the third i.p. dose of dengue type 2 virus (DV) protected recipient mice against intracerebral challenge with DV, whereas the serum obtained after 1 and 2 weeks provided minimum protection. Adoptive intravenous transfer of immune spleen cells obtained from mice 1 to 5 weeks after immunization did not protect recipient mice against even a small dose (10 LD50) of DV. Depletion of T-cells by treatment of mice with anti-thymocyte serum did not potentiate DV infection. Development of a cell-mediated immune response (CMI) against DV was noted only at two periods by the leucocyte migration inhibition test (LMI), with borderline values of 20 and 21%. Dengue virus did not cause illness or death in mice when given by i.p. or i.v. routes and this was not affected by pre-treatment of mice with silica to damage local macrophages. It is concluded that humoral antibody plays a critical role in recovery from primary dengue virus infection of mice whereas CMI and macrophages appear to have no protective role.