Preferential sensitivity of specific genes in chromatin to the action of bleomycin [an antitumor agent] in different cell types [hen erythrocytes and oviduct cells] was investigated using restriction enzyme digestion of DNA from drug-treated nuclei in combination with the Southern blotting procedure. The highly active ovalbumin gene in laying hen oviduct nuclei apparently is more sensitive than the inactive globin gene to the digestion by bleomycin. In red blood cells, bleomycin preferentially destroys the globin gene but not the ovalbumin gene. Bleomycin, like nucleases, can preferentially destroy DNA sequences in chromatin with open configuration, although the mode of action of this drug on DNA is drastically different from those known nucleases.