The biologic response to pulmonary oxygen toxicity is highly varied, depending on such disparate factors as gestational age, gender, hormonal milieu and nutrition. Studies of the relationship between these biologic variables and classic antioxidant mechanisms have failed to support a causal relationship, leaving the biologic nature of this antioxidant mechanism unknown. Alternatively, cellular triglycerides have been found to act as antioxidants in a number of cell types, including endothelium, epithelium, and fibroblasts, both in vivo and in vitro. Our studies of the ontogeny of fetal rat lung fibroblast TG metabolism have revealed that it is regulated by both glucocorticoids and androgens which increase or decrease the TG content of these cells in utero. For example, there is a 5-fold difference between day 18 and 21 fibroblast TG content and a 73±17% difference between day 20 male and female fibroblasts, resulting in significant differences in survival of these cells when challenged with H2O2 (50 v. 97% (p<.01), 47 v. 82% (p<.01), day 18 v. 21, male v. female, respectively. To directly test the antioxidant effect of TG, day 19 FRLF were treated with DEX (1×10-8M) or DEX + DHT(1×10-7M) and challenged with H2O2. Steroid treatments per se had no effect on cell survival; however, 24 hour exposure to 20% serum resulted in significant differences (control 58%, DEX 97%*, DEX + DHT 62%; *p<.01), providing direct evidence that the steroid effect on antioxidant function is TG-dependent. These hormonal effects on the accumulation of extra-cellular TGs provide a unifying mechanism for the seemingly disparate biologic variables (gestational age, gender, hormonal milieu, nutrition) associated with pulmonary oxygen toxicity.