A randomized double-blind study was made in 67 modestly hypercholesterolemic subjects by replacing 50 g of daily dietary fat by the same amount of a rapeseed oil preparation without and with fat-soluble sitostanol esters. The diet became relatively rich in dietary fat (37%) especially in subjects with a low basal calorie intake. The esters were prepared by transesterification of sitostanol with rapeseed oil fatty acids. The effects of sitostanol esters were studied on serum cholesterol and cholesterol synthesis (measuring cholesterol precursors in serum) and absorption (measuring serum plant sterols). The results were related to different apoE phenotypes. A 6-week regimen of about 3.4 g/day of sitostanol lowered total and low density lipoprotein (LDL) cholesterol levels by 7.5% and 10%, respectively, over that due to rapeseed oil alone. High density lipoprotein (HDL) cholesterol and triglyceride concentrations were unchanged. Thus, the HDL/LDL cholesterol ratio was significantly increased. The decrease in LDL cholesterol level was more consistent in subjects with the epsilon 4 allele than in those with homozygous epsilon 3 alleles. Sitostanol markedly decreased serum campesterol (-46%) and sitosterol (-30%), especially in subjects with the epsilon 4 alleles known to have high cholesterol absorption . The decreases of LDL cholesterol and plant sterols were interrelated, suggesting that reduced cholesterol absorption contributed to the lowering of LDL cholesterol. Serum sitostanol was unchanged, while the serum cholesterol precursors, delta 8-cholestenol, desmosterol, and lathosterol, were compensatorily increased by 10% (P < 0.05), most consistently in the subjects with epsilon 4 alleles, indicating an increase in cholesterol synthesis. The study demonstrates that sitostanol esters dissolved in dietary fat can be recommended for treatment of modest primary hypercholesterolemia and are apparently practical and suitable for cholesterol lowering in a general population.