The intracellular level of the c-myc protein is elevated in a dose and time dependent manner by DNA strand breakage. Lesions introduced by either alkylating agents or gamma irradiation are capable of stimulating increased production of c-myc protein. In addition, inhibition of DNA strand break rejoining maintains the level of the c-myc protein in an elevated state, whilst inhibition of DNA replication does not cause an increase in c-myc protein. We conclude that chromatin perturbation via DNA strand breakage both increases the endogenous amounts of the c-myc protein and maintains its elevated level.