The survival response of cultured mammalian cells treated with bleomycin was studied. The dose-response curves of 4 cell lines of different origin exhibited an upward concavity. The true sensitivity of cells, shown by the initial slope, appeared to be slightly different among cell lines, whereas the final slope did not differ appreciably. The fraction of the terminal portion ranged from 30–60% of the population, depending on the cell lines. The inactivation of the mouse L cells, determined as a function of time of the treatment, was biphasic, with the inflection point during the first 60 minutes. The inactivation constant of the terminal resistant portion increased with greater concentration of bleomycin, though not directly proportional to the increase. The interpretation of the biphasic survival response was that bleomycin inactivated cells exponentially and then induced the resistance of cells as the time of incubation elapsed. This was evidenced by a two-dose fractionation experiment in which the induced resistance disappeared within 2–4 hours after the antibiotic was removed. It was concluded that bleomycin not only exerts a lethal effect on but also induces resistance in mammalian cells. From these findings, a chemotherapeutic scheme of bleomycin was proposed.—J Natl Cancer Inst 49: 1093–1100, 1972.