The effects of perfused oleic (18:1n-9), arachidonic (20:4n-6) and 5,8,11,14-nonadecatetraenoic (19:4n-5) acids on triglyceride and cholesterol secretion and ketone body production were studied in isolated rat liver. As compared to oleic and 19:4n-5 acids, both ketone body production and triglyceride secretion were significantly lowered when arachidonic acid was perfused. The concentration of triglyceride in the post-perfused liver was lower upon perfusion with arachidonic acid than upon perfusion with oleic acid or 19:4n-5 acid. Cholesterol secretion in the liver perfused with arachidonic acid or 19:4n-5 acid was significantly higher than with oleic acid. The concentration of cholesterol in the post-perfused liver was slightly but significantly higher with 19:4n-5 acid than with the other fatty acids. The results suggest that 19:4n-5 acid when compared with arachidonic acid affects lipid metabolism in liver differently.