The metabolism of [1-3H]retinol- and [4-14C]cholesterol-labeled chylomicrons was studied in normal and cholesterol-fed dogs in order to estimate the relative contribution of chylomicron remnant cholesterol to diet-induced hypercholesterolemia. The plasma t 1/2 of intravenously administered Sf greater than 400 chylomicrons, Sf 20-400 chylomicrons, and whole lymph doubly labeled with [1-3H]retinol and [4-14C]cholesterol was not significantly prolonged in hypercholesterolemic recipients. When Sf greater than 400 chylomicrons were administered intravenously, 90% of the radioactivity was cleared from the plasma of both normal and cholesterol-fed dogs within 1 hr and 68 +/- 18% appeared in the liver within approximately 2 hr in normal dogs and 4 hr in hypercholesterolemic dogs. The use of the retinol-labeling technique for intestinal lipoproteins provided evidence that some LDL, but essentially none of the HDLc, was derived from d greater than 1.006 g/ml lymph lipoproteins. The failure of significant radioactivity to accumulate in the plasma compartment of hypercholesterolemic dogs after intravenous administration of doubly labeled chylomicrons and the relatively efficient uptake of radioactivity by the liver indicate that the dietary-induced hypercholesterolemia in dogs is not the result of impaired hepatic removal of chylomicron remnants.