Rats were fed either cholesterol-free or high-cholesterol (1%, w/w) semipurified diets containing acetate (0.5%) or cholestyramine (0.44%) or both compounds for 29 days. The bile-acid binding resin, cholestyramine, did not affect serum and liver cholesterol, irrespective of whether the diet was cholesterol-free or contained cholesterol. In the cholesterol-free diets, acetate tended to lower the concentration of serum cholesterol, but did not influence liver cholesterol. When the diets contained cholesterol, acetate lowered liver cholesterol concentrations by about 20% both in the presence and absence of cholestyramine. Acetate did not affect the excretion of bile acids in feces. The mechanism by which acetate may partly counteract the increase in liver cholesterol seen after cholesterol feeding of rats, remains to be established.