The importance of antibody and CD8⁺cells in resolution of murine rotavirus (EDIM) infection and protection against reinfection was examined with two strains of B-cell-deficient mice. Following inoculation of one strain (J_HD), rotavirus infection was resolved within days, but when later reinoculated with EDIM, these mice again shed rotavirus. Thus, effector mechanisms other than antibody resolved viral shedding in J_HD mice but were insufficient to prevent reinfection. EDIM shedding in another B-cell-deficient mouse strain (μMT) diminished but was not fully resolved 93 days after the initial infection, thus demonstrating that antibody could also be important in resolution of rotavirus infection. When depleted of CD8⁺cells by monoclonal antibody treatment before EDIM inoculation, J_HD mice were unable to resolve shedding. Even though μMT mice did not fully resolve their initial infection, depletion of CD8⁺cells 49 days after initial inoculation resulted in a burst of shedding. Thus, CD8⁺cells were involved in resolution of the initial EDIM infection in both strains of B-cell-deficient mice. Finally, when μMT mice were depleted of CD8⁺cells before the initial EDIM infection, gradual resolution of rotavirus shedding was still observed, suggesting a third effector mechanism was also involved in resolution of rotavirus infection in mice.