The Basic Protocol in this unit describes an assay for murine IFN-induced antiviral activity and employs vesicular stomatitis virus (VSV) and IFN-sensitive fibroblasts. Support Protocol describes the preparation of VSV cultures and the calculation of multiplicity of infection (MOI; i.e., concentration of viral particles required to infect cells). Support Protocol describes the antibody neutralization assay, which can be used to identify the bioactive species of IFN in a sample, or to test the potency of an antibody preparation against a particular species of IFN. Alternate Protocol 1 covers measurement of human IFN-induced antiviral activity; while the steps are quite similar to Basic Protocol, different viral and cell cultures are described.