The consumption of long chain polyunsaturated fatty acids by fish oils leads to profound lowering of plasma triacylglycerol but not of plasma cholesterol. Reasons for this were investigated with the human hepatoma cell line, the Hep G2 cell. Incubations with oleic acid (18:1 n9), linoleic acid (18:2 n6) and the characteristic marine fatty acid eicosapentaenoic acid (EPA, 20:5 n3) enriched cellular triacylglycerol mass, though least with EPA. However, secretion of very low density lipoprotein (VLDL) triacylglycerol and apoprotein B (measured by formation from [3H]glycerol and [3H]leucine) was markedly inhibited by EPA. Preincubation with linoleic acid reduced VLDL triacylglycerol but not apo B secretion in comparison with oleic acid which stimulated both. A possible effect on low density lipoprotein (LDL) removal was studied by measuring [125I]LDL binding. Preincubation with either EPA or linoleic acid inhibited the saturable binding of LDL, observed with oleic acid and control incubations. The binding of lipoproteins containing chylomicron remnants was not affected by any of the fatty acids.