Growth promoting activity of bovine serum albumin for human diploid fibroblasts was affected by oxygen environment. When cells (2 X 10(4) cells/35 mm dish) were cultured with BSA of 5 g/liter supplemented RITC 80-7 under hypoxic (7%) environment, excellent growth was maintained during the period of culture, while the growth under aerobic environment markedly declined after 3 days of culture. The culture challenged with BSA under aerobic environment generated a relatively large amount of malondialdehyde (MDA) as a product of lipid peroxidation. Vitamin E restored the declining of growth and inhibited MDA formation. Also in vitro lifespan of the cells challenged with BSA markedly decreased under aerobic environment as compared with that of the cells under hypoxic environment. Vitamin E did not restore the oxygen-dependent decreasing of in vitro lifespan. On the other hand, the cells cultured with serum supplemented medium grew and phased out similarly under both oxygen environment as well as the case with BSA supplemented RITC 80-7 under hypoxic environment. These results suggest that the extent of cell proliferation is controlled in part by lipid peroxidation and serum antioxidant activity is not identical from that of vitamin E.