Research on endotoxin protection from oxygen toxicity is presently limited to the rat model since only rats have been protected by endotoxin. This study reports that endotoxin also extends survival of adult male mice in hyperoxia (> 99% oxygen at 1 ATA). Initially, 4-month-old male mice were treated with Boivin-extracted E. coli endotoxin and placed in hyperoxia. Zymosan-primed mice receiving 2 or 10 yg endotoxin, and unprimed mice receiving 10-40 yg endotoxin, showed moderate protection against hyperoxia; 11/15 Boivin-treated mice survived 120 hours exposure to hyperoxia with time-of-death in hyperoxia = 126.7 ±4.4 hours (mean ± SEM, n=15). This contrasts with untreated male mice; 0/4 survived 120 hours exposure to hyperoxia with mean survival = 103.5 ± 3.5 hours. Mice receiving 20 or 60 yg Westphal-extracted endotoxin were not protected nor were older female mice receiving 20 yg Boivin-extracted endotoxin. This study suggests that age, sex, the extraction method used to obtain endotoxin, and possibly the time of year when endotoxin is administered, are important variables in allowing endotoxin to extend survival of mice in hyperoxia.