Intranasally administered alpha/beta interferon blocked extension of the coronavirus, mouse hepatitis virus, strain JHM (MHV-JHM), from the nose to the brain of BALB/cByJ mice following intranasal inoculation with the virus. Two hundred units of alpha/beta interferon were administered intranasally to BALB/cByJ mice daily over a five day period. The mice were exposed intranasally to 10³ median tissue culture infectious doses of MHV-JHM on the third day of interferon treatment. Two days after virus exposure, the proportion of mice with MHV in nasal turbinates was reduced from 10 of 10 in the untreated group to 7 of 10 in the interferon-treated group, and mean titers in virus-containing noses were lower in the interferon-treated group. Five days after virus exposure, the proportion of mice with infectious virus in the brain was significantly lower in the interferon-treated group (1 of 10 mice) than in the untreated group (10 of 10 mice). Systemic infection, as measured by presence and concentration of virus in the spleen, was not affected by intranasal interferon treatment. These results suggest that intranasally administered interferon protects against local extension of MHV-JHM from nose to brain, but not against dissemination of virus to other organs, such as the spleen.