Several strains of foot-and-mouth disease virus (FMDV), types O, A, and C, grown in primary or secondary calf kidney cell cultures had an interferon-sensitivity which varied with incubation temperature. Some wild-type strains growing optimally at 37° C showed an increased interferon-sensitivity at 28° C. Strain CL was more sensitive at both infra- and supraoptimal growth temperature. Temperature-sensitive mutants with optimal replication at 28° C were more sensitive at 37° C. Interferon-sensitivity moreover varied greatly among the virus strains tested even at optimal temperature. Results are interpreted by the hypothesis that the interferon-sensitivity depends on a virus specific product, presumably a protein, with a reduced optimal range of function (compared with virion formation) which acts as “anti-interferon”. Possible relationships with virulence of FMDV and temperature-sensitivity of viral proteins are discussed.