Previous investigation of an animal model of diffuse granulomatous lung disease has shown that moderate hypoxia results in a dramatic fall in oxygen utilization and a rise in lactate production by the diseased lung (1-4). Newman and Naimark have found that severe hypoxia reduces palmitate incorporation by normal lung (5). Their study prompted us to test the effects of moderate hypoxia upon this metabolic activity in the model of granulomatous disease.Methods. Pulmonary granulomatous disease was produced by intravenous injection in dogs of 0.3 ml/kg complete Freund's adjuvant (Difco Laboratories, Detroit, Mich.) on 2 successive days (1). The dogs were studied 3-4 weeks after injection when the disease reaches its maximum extent. Eight normal and eight diseased dogs were studied according to an identical protocol. The dog breathed the appropriate gas mixture (FIO2 0.14-0.25) until he attained a steady level of ventilation. Five-tenths millicurie in 1.3 mg of crystalline [ l-14C]palmitic acid (New England Nuclear Corp . , Boston, Mass .) were then given intravenously. Arterial blood samples were collected from the femoral artery at 20, 40, and 60 min for measurement of oxygen and carbon dioxide tension and pH using an Instrumentation Laboratory blood gas analyzer. At 1 hr after administration of labeled palmitate, the dog was exsanguinated by transection of the femoral arteries.The lungs were promptly removed, weighed, and immersed in 2:l (v/v) chloroform-methanol at -20°, then homogenized, stirred, and filtered. The filtrate was washed with 0.37% KCl (20 m1/100 ml filtrate), centrifuged, and the supernatant was collected. The washing was repeated twice with 0.74 % KC1-chloroform-methanol solution in a volume ratio of 47 :3 :48 , respectively.The washed lipid extract was dried and redissolved with petroleum ether to a volume of 500 ml. This comprised the stock solution from which all subsequent analyses were made. Four milliliters of the stock solution were dried under nitrogen, redi,ssolved in chloroform, and put through ll)-cm Kimax columns containing 2 g of silicic acid (325 mesh). Three subsequent washings of 10 ml of methanol eluted the phospholipids which were collected in preweighed vials, dried under nitrogen, and reweighed. Total lipid recovery from the columns, as determined by radioactivity recovered, was 80 % for both the normal and diseased specimens.Additional aliquots of the stock solution were similarly prepared for counting and fractionation. Counting was done with a Packard Tri-Carb liquid scintillation counter. Separation was done by thin-layer chromatography with silica gel H, using chloroform-methanol-water-glacial acetic acid, 80:25:4:1 (v/v) as the solvent. The plates were stained with iodine vapor and the spots were scraped separately for counting. In addition, the fatty acid composition of phosphatidyl choline was determined in four diseased and four control specimens by gas chromatography.For autoradiographic studies two control and two diseased dogs were studied breathing room air accor...