To study factors controlling plasma cholesterol levels, the effect of dietary fat type on cholesterol synthesis was examined in 15 hypercholesterolemic subjects (low-density lipoprotein [LDL] cholesterol > 130 mg.dL-1) consuming over a period of 32 days (1) a baseline diet (36% kcal as fat: 15% saturated, 15% monounsaturated, and 6% polyunsaturated fat; 180 mg cholesterol.1000 kcal-1) and diets meeting National Cholesterol Education Program step 2 criteria (30% kcal as fat, < or = 7% saturated fat, 80 to 85 mg cholesterol/Mcal), where two thirds of the fat was either (2) olive, (3) corn, or (4) canola oil. Plasma total, LDL, and high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the end of each period. Cholesterol fractional synthesis rate (FSR) was also measured as the deuterium (D) incorporation into plasma total cholesterol relative to body D2O level (1.2 g D2O.kg-1 estimated body water) over 24 hours. Absolute synthesis rates (ASRs) were determined as the product of FSR and rapid turnover cholesterol pool size. Plasma total and LDL cholesterol levels declined significantly (P < .005) on all plant-oil diets compared with the baseline diet; however, triglyceride levels were not different. FSRs were higher (P < .05) for the corn oil (0.0665 +/- 0.0097 pool.d-1) compared with baseline (0.0412 +/- 0.0060 pool.d-1) and olive oil (0.0409 +/- 0.0052 pool.d-1) but not canola oil (0.0492 +/- 0.0072 pool.d-1) diets.(ABSTRACT TRUNCATED AT 250 WORDS)