We found in the segment of this study that lipid peroxides inhibit the proliferation of aortic medial smooth muscle cells derived from rats with streptozotocin-induced diabetes (STZ-rats) and normal cells cultured in an adriamycin-containing medium. It was then supposed that vitamin E, an antioxidant, may restore cell proliferation by its inhibitory effect on lipid peroxides. This led us to study the effect of vitamin E on the proliferation of cells derived from STZ-rats and normal cells cultured in an adriamycin-containing medium. The growth rate of normal cells was increased by the addition of vitamin E. However, its effect was reduced with aging. on the other hand, the growth rate of cells derived from STZ-rats was hardly affected and intracellular synthesis of lipid peroxides was not attenuated by the addition of vitamin E. The effect of vitamin E on cell proliferation and the synthesis of intracellular lipid peroxides was not found in cells obtained 12 months after STZ injection. Adriamycin inhibited normal cell proliferation concentration-dependently with an increase in intracellular lipid peroxides. However, when normal cells were planted in a medium containing adriamycin and vitamin E, the effect of adriamycin on cell proliferation was reduced. Namely, when lipid peroxides coexisted with adriamycin for a short period of time, vitamin E prevented the effect of lipid peroxides on cell proliferation. However, when they remained in the cells for a long period of time, vitamin E did not show any inhibitory effect on the lipid peroxides. The results suggest that the effect of vitamin E on cell proliferation is dependent on the period of intracellular existence of lipid peroxides.