Induction of the antiviral state is probably mediated by secondary messenger molecules that are induced at the cell membrane by interferon, signal the nucleus to produce antiviral protein(s), and by cell-to-cell transfer induce viral resistance in adjacent cells. These findings resulted from coupling two observations. First, many cell types communicate among themselves by gap junctional transfer of metabolites and small control molecules. Second, interferon action shows species preference. It is reasoned that, if induction of the antiviral state is mediated by small secondary molecules, these by gap junctional transfer might influence adjacent cells. This is tested by coculturing two different cell species in the presence of interferon to which only one cell species is sensitive and determining whether the other became resistant to virus infection. It is found that under these conditions the cell species, not directly sensitive to interferon, became resistant to virus infection. The cell-to-cell transfer of viral resistance was initiated by interferon, is rapid, and required ongoing RNA synthesis in the recipient cell. This process represents a major amplification system for interferon action. © 1981, Academic Press, Inc.