To investigate the influence of the dietary protein level on plasma cholesterol homeostasis and lipoprotein susceptibility to peroxidation, rats were adapted to semi-purified diets with different levels of casein (8, 16, or 32%). Increasing the dietary protein level had a positive influence on the plasma and liver availability of sulfur amino acids, as well as on taurine and glutathione concentrations. Rats fed the protein-deficient diet (8%) exhibited a slight hypercholesterolemia, together with an induction of liver 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase and a low activity of fatty acid synthase, compared with controls (16% casein diet). In contrast, feeding high-protein diets resulted in a cholesterol-lowering effect together with a lowered activity of liver HMG CoA reductase. The susceptibility of isolated lipoprotein (VLDL + LDL) fractions to copper-induced oxidation was also investigated: there was a shortened lag time period for conjugated diene production in rats fed the 8% casein diet. Thus, with a protein-deficient diet, a slight hypercholesterolemia could be aggraved by a high susceptibility of lipoprotein to peroxidation, probably because of a limiting bioavailability of sulfur amino acids in plasma and a depletion of intracellular glutathione and taurine.