The effect of an increased polyunsaturated fatty acid concentration in the diet on the plasma lipoproteins from a normal group of healthy persons and from a group of hypercholesterolemic patients, consuming an isoenergetic and an isocholesterolemic diet, was examined and the changes in the plasma phospholipids were measured. Nine normal and 10 hypercholesterolemic patients were treated with a polyunsaturated diet for 1 month. Controls and hypercholesterolemic patients were screened on their lipid and lipoprotein profiles and their P/S ratio in the diet was calculated and increased with a factor 4. In the control group the P/S ratio was increased from 0.35 to 1.38 and in the hypercholesterolemic group from 0.46 to 1.59. They received the diet for at least 4 weeks before a second analysis of lipids and lipoproteins. The most important results are a decrease of plasma cholesterol, followed by a significant increase of HDL cholesterol. The cholesterol-lowering effect results largely from the plasma LDL decrease, especially in the patient group. Apo A-I is decreased accompanied by a significant increase of the ratio HDL-C/apo A-I. The observed changes are most pronounced in the hypercholesterolemic group. There is no change in apo B but a significant change in the linoleic acid concentration especially in the HDL cholesterol esters. The major phospholipids in plasma are identical in both groups and there is an identical change under the PUFA diet, sphingomyelin is increased and phosphatidylcholine is decreased, which may be related to an increase of the HDL2/HDL3 ratio.