The presence of a factor that regulates plasma arachidonic acid which is distinct from the pancreatic enzymes has been previously demonstrated in the external pancreatic secretion of the dog and pig. The present study was undertaken to determine if the factor is present in man. The fatty acid percentage composition of plasma total esterified, phospholipid, cholesterol ester, triglyceride and unesterified fatty acid fractions was analyzed by gas -liquid chromatography, and the absolute levels (mg/100 ml) of each fraction were determined in patients with pancreatic cystic fibrosis, Laennec''s cirrhosis and hepatitis. These were compared with the levels of groups of normal children and adults. Characteristic alteration of the percentage composition of the plasma fatty acids was observed in pancreatic cystic fibrosis. Palmitic, palmitoleic and oleic acids were elevated with concomitant depression of linoleic andara-chidonic acids. Since hepatomegaly was noted in several of the children, the same study was done on a group with Laennec''s cirrhosis and hepatitis of recent onset. The same changes of the individual plasma fatty acids were seen in all patients with Laennec''s cirrhosis, and were of greater magnitude. The changes in the hepatitis group paralleled those of Laennec''s cirrhosis, but were of lesser degree in the latter and in pancreatic cystic fibrosis. It was concluded that the plasma fatty acid changes in pancreatic cystic fibrosis were due to accompanying liver disease. It appears that the incidence of hepatic cirrhosis (80%) is far greater in pancreatic cystic fibrosis than previously reported from postmortem studies (25%). The cholesterol ester fraction appeared to be the most sensitive indicator of liver disease.