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Cystic fibrosis (CF) is associated with deficiencies in certain essential fatty acids. These deficiencies have been studied in plasma, red blood cells, and mucus and were previously thought to be a result of malnutrition or malabsorption. More recent studies have indicated that these deficiencies are independent of nutritional status. However, these studies examined fatty acids in plasma but not in CF–regulated tissues. In the pancreas, lungs, and ileum of CF knock-out mice, membrane-bound arachidonic acid levels have been shown to be increased while docosahexaenoic acid levels are decreased. This lipid abnormality is reversed following oral administration of docosahexaenoic acid (DHA). In addition, DHA therapy reverses the increased neutrophil infiltration in the lungs of CF knock-out mice. Further studies are required to determine the mechanism by which CF gene mutations lead to this lipid abnormality.