Nude mice which had received intraperitoneal injection of silica simultaneously with infection of mouse hepatitis virus, NuU strain, died of severe necrotic hepatitis within 2 weeks postinfection, whereas those having received no silica survived for 3 weeks or more after challenge. Silica given day 4 postinoculation had no effect. The virus titers of the liver and spleen at day 4 as well as serum interferon levels at day 2 were much higher in silica-treated mice than those without silica treatment. At day 2 or 3 postinoculation, silica-treated mice were found to have a considerable number of necrotic foci in the liver with some neutrophil and lymphocyte infiltration, and viral antigen was present in the cytoplasm of some hepatocytes around necrotic foci. In contrast, those without silica treatment showed only some necrotic foci with some lymphocyte infiltration. Viral antigen was detected only in a few littoral cells but not in hepatocytes. The role of macrophages in the resistance at early stage of infection in nude mice is discussed.