Survival of mice after Klebsiella pneumoniae infection and phagocytosis by alveolar macrophages (AMs), in the presence or absence of ozone (O(3)) exposure prior to infection, is sex dependent. The objective of this work was to study the role of gonadal hormones, 5α-dihydrotestosterone (DHT) and 17β-estradiol (E(2)), on mouse survival after filtered air (FA) or O(3) exposure. Gonadectomized female (G×F) and male (G×M) mice implanted with control or hormone pellets (DHT in G×F, or E(2) in G×M), exposed to O(3) (2 ppm, 3h) or FA, and infected with K. pneumoniae were monitored for survival. Survival in G×F was identical after FA or O(3) exposure; in G×M O(3) exposure resulted in lower survival compared to FA. In O(3)-exposed females, gonadectomy resulted in increased survival compared to intact females or to G×M+E(2). A similar effect was observed in G×F+DHT. The combined negative effect of oxidative stress and hormone on survival was higher for E(2). Gonadectomy eliminated (females) or minimized (males) the previously observed sex differences in survival in response to oxidative stress, and hormone treatment restored them. These findings indicate that gonadal hormones and/or oxidative stress have a significant effect on mouse survival.