To investigate the role that defective interfering (DI) particles might conceivably play in the epizootiology of vesicular stomatitis, two virulent New Jersey (NJ) isolates from the 1982-1983 epizootic in the United States (US) were compared with three laboratory adapted strains of vesicular stomatitis virus (VSV): NJ Hazelhurst, NJ Ogden and Indiana San Juan. Successive undiluted passages showed that the virulent isolates did not readily exhibit 'autointerference' because they did not readily generate and amplify DI particles. Viral RNA synthesis of isolates that were exposed to homotypic or heterotypic DI particles generated from the laboratory strains showed that the isolates were totally resistant to the heterotypic DI particle and partially resistant to the homotypic DI particle. In contrast, Indiana San Juan and NJ Ogden were inhibited by hetero- or homotypic DI particles. NJ Hazelhurst more closely resembled the isolates. This demonstrates that virulence of VSV in its natural setting may be related to a number of factors, including the slower generation and amplification of endogenous DI particles, as well as the increased resistance of the virus to some pre-existing DI particles.