SummaryMice were inoculated ic with CG-179, a strain of NDV which by this route causes 100% lethal encephalitis within 9 days, and with Hickman, a strain which is avirulent by this route. Measurement of interferon activity in the brain at daily intervals following inoculation revealed that following CG-179 two peaks of activity occurred—one at 24 hr and the other at 120 to 144 hr. This unusual biphasic response did not occur in the brains of mice inoculated with Hickman strain. In these mice interferon activity in the brain peaked at 24 hr and then disappeared rapidly. Neither infective virus nor viral antigen could be detected in the brains after inoculation with either strain. There appeared to be no difference between viral strains in the order of magnitude of the first peak of interferon activity. No biphasic activity was detected in spleens or sera of mice after either ic or iv inoculation of CG-179. Possible differences between the 2 strains of NDV are discussed as well as possible explanations for ...