The direct action of ozone on viability and survival of normal and modified mouse lung fibroblasts has been studied. By cell manipulation of fibroblasts in culture, the content of polyunsaturated fatty acids (PUFA) in the phospholipids was increased from about 6% to about 40%. The cellular content of α‐tocopherol (α‐T) (vitamin E) could be drastically enhanced. Vitamin E supplementation to the cell did not subluence the PUFA manipulation. Normal, PUFA, and PUFA(α‐T) fibroblasts were exposed to ozone by bubbling 10 ppm through the cell suspensions for different periods of time (0–6 h). No significant effects of the ozone exposure could be established when normal fibroblasts were used. The PUFA fibroblasts, however, were very vulnerable to ozone toxicity, both in terms of dye uptake (Trypan blue) and cell death (clonogenic ability). When α‐tocopherol was present in the cell (200 ng/106cells), a clear protection against ozone toxicity was found.