Sera from 10 patients with essential hypercholesterolemia on ad libitum diet have been analyzed for their content of polyunsaturated fatty acids in the cholesterol esters and the results compared with a matched group of normal subjects. Three cases were analyzed after corn oil substitution for other fats in the diet, and 2 of them were analyzed after addition of pyridoxine to the corn oil regimen. One patient was followed 18 months, and during that time he received a large dosage of corn oil.Patients with essential hypercholesterolemia had an absolute increase in the amount, but generally a lower percentage content of dienes in their cholesterol esters than normals. After the change to corn oil, the content of polyunsaturated fatty acids increased to levels sometimes considerably above those in the normal subjects, although the total serum cholesterol in one of these cases was by no means normalized. The addition of 100 mg. of pyridoxine to the corn oil regimen did not produce any further decrease in the serum cholesterol level and did not produce any changes in the fatty acid fractions.The absolute increase in the amount of polyunsaturated fatty acids in the cholesterol esters in essential hypercholesterolemia, particularly after an extremely high intake of unsaturated fat, speaks against factors causing an inhibition in esterification with polyenes as being of central importance.