The mechanism of change in low-density lipoprotein (LDL) levels by diets differing in fat saturation have been studied. Turnover of 125I-LDL was measured in eight subjects with type II hyperlipoproteinemia and in seven normal control subjects during two dietary periods containing 40% of calories as either safflower oil (polyunsaturated fat, PSF) or as lard (saturated fat, SF). Higher levels of LDL apoprotein and LDL-cholesterol were observed in both groups on saturated fat. Subjects with elevated LDL levels (type II) showed a more marked effect of polyunsaturated fat with 25% lower LDL production rate as compared to a reduction of only 10% for the control group. On the PSF diet, the production rate in type II (12.7 mg.kg-1.day-1) was not statistically different from normal subjects (10.5 mg.kg-1.day-1). On this diet, the higher levels of LDL cholesterol in the type II subjects (as compared to controls) were due to a lower fractional clearance rate, mean of 0.27/day compared to a mean of 0.39/day for the normal subjects. Although individuals with type II hyperlipoproteinemia may have a primary clearance defect, the major reduction in plasma cholesterol concentrations achieved with a diet high in polyunsaturated fat can be attributed to a significantly lower LDL production.