. Estrogen pretreatment protects males against hypoxia-induced immune depression. Am J Physiol Cell Physiol 282: C1087-C1092, 2002. First published December 12, 2001 10.1152/ajpcell.00454.2001.-Hypoxemia depresses cell-mediated immune functions in males, whereas proestrous females do not show such a depression. We hypothesized that elevated systemic estradiol levels in proestrous females prevent hypoxemia-induced immune depression. To study this hypothesis, male C3H/HeN mice were pretreated with 17-estradiol (E 2, 40 g/kg body wt sc) or vehicle for 3 days before induction of hypoxemia and again immediately before induction of hypoxia. The mice were subjected to hypoxemia (95% N 2-5% O2) or sham hypoxemia (room air) for 60 min, and plasma and spleen cells were collected 2 h later. In vehicle-treated mice, splenocyte proliferation and interleukin-2 and interleukin-3 production were depressed after hypoxemia. E 2-pretreated animals, however, displayed no such depression in splenic T cell parameters after hypoxemia. Splenic macrophage cytokine production was also depressed in vehicle-treated mice subjected to hypoxia, whereas it was normal in E 2-pretreated mice. In summary, these findings indicate that administration of E 2 before hypoxemia prevented the depression of cell-mediated immune functions. Thus administration of 17-estradiol in high-risk patients before major surgery might decrease hypoxemia-induced immune depression under those conditions.