Exposure of rats and mice to hyperoxia decreases lung coenzyme A (CoASH) contents, with a decrease of 50% observed in adult male Fischer-344 rats exposed to >95% O(2) for 48 h. Decreases in lung CoASH levels are not accompanied by increases in contents of the mixed glutathione disulfide of CoA, as might be expected of a primary oxidative stress on CoASH status. Animals exposed to hyperoxia exhibit decreased food intake, and the present studies were to test the hypothesis that fasting would decrease lung CoASH contents, thereby suggesting a mechanism for the effects of hyperoxia. Adult male Fischer-344 rats were examined after 0, 24, or 48 h of fasting (n = 5, 6, and 6, respectively). Fasting for 24 or 48 h did not affect lung CoASH levels or lung weights, despite 6 and 12% losses in body weight. Lung glutathione concentrations (nanomoles per gram of tissue) and contents (nanomoles per whole organ) and glutathione disulfide contents were 10 to 20% lower in rats fasted for 48 h than in fed rats. Liver weights and glutathione and glutathione disulfide contents and concentrations were 30 to 70% lower in rats fasted for 24 or 48 h than in fed rats. Hepatic CoASH concentrations increased during fasting, but hepatic contents of CoASH remained remarkably constant. Liver protein contents (milligrams of protein per whole organ) decreased after 24 and 48 h of fasting, but protein concentrations (milligrams of protein per gram of tissue) were higher in rats fasted 48 h than in fed rats. Overall, glutathione, glutathione disulfide, and protein contents in liver and skeletal muscle decreased with fasting, but significant changes in CoASH contents were not observed. Diminished food intake in animals does not explain the effects of hyperoxia on lung CoASH contents. CoASH and derived thioesters participate in many cellular functions, and if depletion of lung CoASH during hyperoxia proves to be relevant to mechanisms of lung injury, support of mechanisms needed to sustain CoA levels could be helpful in prematurely born infants and in adults.