Infection of interferon-treated L-929 mouse fibroblasts with vaccinia WR virus is followed by severe cytolysis within 3 to 4 h. It is shown that this cytolysis cannot be caused by enzymes released from lysosomes into the cytosol. However, there is evidence that homologous interferon has a noxious effect on lysosomes. This phenomenon appears to be another aspect of the anticellular functions of interferon.