The herpes simplex virus virion protein Vmw65 trans activates the viral immediate-early genes and some octamer-containing cellular genes, including that encoding histone H2B. We found, however, that a truncated form of this virion protein repressed H2B gene transcription and also dominantly inhibited induction of the gene by intact Vmw65. A cell line expressing this truncated protein expressed reduced levels of H2B and grew more slowly than the parental cell line or a similar line expressing the intact protein.