Previous studies demonstrated a protective effect of hypoxia on subsequent death breathing oxygen. Four groups of rats were exposed to air for 120 hours plus 99% O2 for 52 hours (A + O2); 120 hours of hypoxia plus 52 hours 99% O2 (H + O2); 172 hours of only air (A); and 120 hours of only hypoxia (H). Rats were sacrificed and lung lavage protein (gm/ 100 ml) was 0.57 +/-0.18 in A + O2 and 0.26 +/- 0.12 in H + O2. Hematocrits were increased at sacrifice. Rats with induced hematocrits of 61% did not have a protective effect breathing oxygen. Mean total phospholipid in lung lavage was: A + O2 O.94; H + O2 1.10; A 1.08; and H 1.76 (micronM/ml). Phosphatidyl choline (lecithin) was: A + O2 0.49; H + O2 0.61; A 0.59; and H 1.15 micronM/ml. Differences among the groups were significant for total phospholipids and phosphatidyl choline except between air (A) and hypoxia + O2 (H + O2). Palmitic acid was decreased in A + O2 compared to the other groups. Oxygen breathing results in decreased total phospholipids and phosphatidyl choline in lung lavage. Pretreatment with hypoxia and subsequent oxygen breathing results in amounts similar to rats breathing air only.