Adult rats exposed to hyperoxia are protected from lung injury by treatment with bacterial endotoxin. Experiments were undertaken to determine whether endotoxin treatment produces a mitogenic effect on the lung. Endotoxin treatment caused a significant (P less than .05) loss of body weight (8%) in rats exposed to either air or greater than 95% O2 for 24 hr. Therefore, experiments were also undertaken in which both saline- and endotoxin-treated rats were starved for the duration of the experiments to make equal any nutritional imbalance. The rate of DNA synthesis in lung slices from fed rats treated with endotoxin did not differ from that of saline-treated controls. In contrast, lung DNA synthesis in starved rats treated with endotoxin increased 50%. The effect of endotoxin treatment was similar in rats breathing air or greater than 95% O2, and lung protein synthesis generally paralleled lung DNA synthesis. These results indicate that endotoxin does exert a mitogenic effect on the lung and this effect can be masked by the nutritional imbalance resulting from endotoxin administration.