Fish oils rich in n - 3 fatty acids (FAs) have been shown to markedly lower levels of very low density lipoproteins (VLDL), but not the low density lipoproteins (LDL) which are derived from VLDL. Changes in the size and chemical composition of lipoproteins may affect their metabolism. In order to examine the effects of n - 3 FAs on lipoprotein metabolism, 6 patients with hypertriglyceridemia were given 6 g n - 3 FAs/day. Plasma lipid and apoprotein (apo A-I, A-II, B, E, C-II, C-III) levels (mg/dl) were measured before and after 4 weeks of treatment. Changes in lipoprotein size were assessed by gel chromatography. n - 3 FAs lowered VLDL cholesterol (58 +/- 35 to 40 +/- 30, P less than 0.01) and total triglyceride (410 +/- 170 to 236 +/- 114, P less than 0.01). In spite of this, LDL cholesterol levels did not decrease, and apo B levels increased (98 +/- 28 to 111 +/- 27, P less than 0.05). HDL cholesterol rose (31 +/- 5 to 34 +/- 7, P less than 0.05). The lipid content of smaller VLDL particles was reduced by over 40%, but the protein content was largely unchanged. Large triglyceride-rich lipoprotein particles were reduced to a greater extent than were small particles. These changes in VLDL particle size and composition may enhance the synthesis of LDL in hypertriglyceridemic patients taking n - 3 FA supplements.