Normal adult A strain mice are resistant to MHV-3 infection. A strain mice immunosuppressed by 600 rads of x-irradiation or by anti-lymphocyte serum treatment became susceptible to the virus and died with specific lesions of the liver and high virus titers. However, mice immunized with MHV-3 before sublethal x-iraddiation resisted a second injection of virus. Resistant adult (A times C3H) F-1 hybrids undergoing graft-vs-host (GVH) reaction became highly susceptible to MHV-3 injected 8 days after parental cell injection. Virus titer 3 days after injection was 2 logs higher in mice undergoing GVH than in controls. However F-1 hybrid mice resisted virus challenge when the first injection of virus was given 2 weeks before GVH induction. In addition, thymectomy also modified the behavior of resistant animals toward virus infection. It appears, therefore, that cell-mediated immune functions play an important role in resistance of mice to MHV-3.