Forty healthy volunteers were allocated in a double blind, randomized study to receive either 20 g of n-3 polyunsaturated fatty acids (PUFA) or 20 g of n-6 PUFA at their evening meal. The effect on plasma lipids and lipoproteins of this single dose of fish oil vs. corn oil was studied the next morning, 14 h after ingestion. Plasma triglycerides and very low density lipoprotein-cholesterol significantly decreased (33%) after n-3 PUFA (P < 0.001), and significantly (P < 0.01) more than after intake of n-6 PUFA. The decrease in plasma triglycerides after n-3 PUFA ingestion was more pronounced in subjects with higher baseline levels of triglycerides (P < 0.001). Total cholesterol decreased after both supplements, but did not differ between the supplements. Low density lipoprotein-cholesterol did not change, and high density lipoprotein-cholesterol significantly decreased in subjects given n-3 PUFA compared to baseline, but not when compared to subjects receiving n-6 PUFA. In conclusion, we have shown that a single very high dose of n-3 PUFA has a pronounced hypotriglyceridemic effect, which is directly related to the initial plasma level.