The effect of very low levels of dietary long-chain n-3 fatty acids on Delta 6 desaturation of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and on Delta 5 desaturation of dihomo-gamma-linolenic acid (20:3n-6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n-3 fatty acids per 100 g of diet were compared to those led the same amount of alpha-linolenic acid. Low amounts of long-chain n-3 fatty acids greatly inhibited Delta 6 desaturation of 18:2n-6 and Delta 5 desaturation of 20:3n-6, while Delta 6 desaturation of 18:3n-3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids was reflected in a decrease in arachidonic acid (20:4n-6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20:4n-6 during fish oil ingestion. Docosahexaenoic acid (22:6n-3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart and kidney phospholipids.