This study was designed to define the effect of dietary restriction and cholesterol feeding on disturbances of very low density lipoprotein (VLDL) catabolism. Three groups of 15 New Zealand rabbits were fed standard or cholesterol-rich diets either ad libitum or in restricted amounts and in vitro binding assays on hepatocyte membranes were carried out after 4, 8, 12 and 20 d. Cholesterol feeding reduced the specific binding of labeled beta-VLDL to liver membranes. Dietary restriction, which enhances the hypercholesterolemia induced by cholesterol feeding, had no additional effect on the down-regulation of beta-VLDL specific binding. In another set of experiments the uptake of labeled beta-VLDL by various tissues was measured after 15 d of feeding the diets. Cholesterol feeding decreased uptake of these lipoproteins by the liver and various extrahepatic tissues, such as skin, intestine, muscle, adipose tissue, kidneys, spleen and aorta. Additional changes occurred in liver and intestine with dietary restriction. In liver beta-VLDL uptake in the group fed a restricted amount of the cholesterol-containing diet was 70% of that in the group fed the same diet ad libitum. Taken together, the results suggest that dietary restriction acts mainly on the receptor-independent catabolism of beta-VLDL.