1. After intracerebral injection or nasal instillation of vesicular stomatitis virus in young or old mice, there was no evidence of a generalized, systemic or blood infection. 2. Within 1 hour after nasal instillation of as much as 100,000 M.C.L.D. in young or old mice, no virus (i.e., less than 60 to 70 M.C.L.D.) could be demonstrated in the nasal mucosa. 2 days later and thereafter virus was abundant in the nasal mucosa of young mice, while among old mice it remained undemonstrable in some and present in small amount in others. 3. Virus was not detected in the anterior rhinencephalon of young and old mice within a few minutes and 5 hours after nasal instillation, but was almost uniformly demonstrable in this region, although not in the rest of the brain, on the 2nd day. This indicated that the primary invasion of the brain occurred by the olfactory rather than the fifth nerve pathway. 4. The essential difference in the further pathogenesis of the disease between the young mice which succumb with encephalomyelitis (5th day) and the old mice which survive without showing clinical signs of brain involvement, is in the progression of the virus from the anterior rhinencephalon. In the young the rest of the brain is invaded, while in the old resistant mice it is not, the progression of virus being arrested somewhere in the anterior rhinencephalon. 5. Since minimal amounts of virus injected intracerebrally were shown to be disseminated quickly through the entire brain, killing old as well as young mice, it was clear that virus so inoculated must spread differently from that which reaches the brain by the olfactory pathway. 6. That the arrest of virus progression in the brains of certain old mice is the result of a preexisting, localized barrier, developed with age, and is not due to a rapidly acquired, specific, cerebral immunity was shown by the failure of old mice to resist an intracerebral injection of 1 to 10 M.C.L.D., 2, 3, 4, or 5 days after preliminary nasal instillation.
