Summary: A virulent and an attenuated strain of foot-and-mouth disease virus were compared in surviving cultures of bovine tongue epithelium for efficiency of titration, production of infective centers after virus adsorption, virus multiplication and interferon production. Titers of the virulent strain measured in unweaned mice were twice those measured in BTE cultures whereas titers of the attenuated strain were 50 times less in BTE cultures than in mice. Production of infective cell centers after virus adsorption was 24 times less efficient with the attenuated strain than with the virulent. In growth curve studies the virulent strain gave rise to higher virus titers than the attenuated strain but produced less interferon. Measurable interferon was detected in cultures infected by the attenuated strain after a certain level of virus had been reached. These differences in behavior can be used to provide markers for laboratory studies of foot-and-mouth disease virus strains. The results were discussed in relation to virulence and production of lesions by strains of foot-and-mouth disease virus. It is suggested that only 5% of the attenuated strain of FMDV was competent, i.e., able to initiate successful infection of the bovine tongue epithelial cells with production of new virus, of which only 5% in its turn was competent. The other 95% noncompetent virus entered the cell, inducing cellular resistance and production of interferon—leading to suppression of virus multiplication and arrest of lesion development.