When either actinomycin D or puromycin is added to cell cultures at the time of infection with herpes simplex virus, or 1 hr later, there is an inhibition of chromosomal damage induced by virus. On the other hand, cytosine arabinoside considerably potentiates the capacity of herpes simplex virus to induce chromosomal damage. This finding supports the view that chromosomal changes induced by virus are probably due to the action of early enzymes controlled by virus genes.