The concept that an absence of apoprotein B in plasma may result in increased cholesterol biosynthesis was investigated by sterol balance techniques in 2 male patients with abetalipoproteinemia, one an adult, the other a child. Total body synthesis of cholesterol in both the adult patient (19.3 +/- 3.8 mg/kg/day vs. 10.8 +/- 0.9 mg/kg/day in controls) and the child with abetalipoproteinemia (34.9 mg/kg/day vs. 14.5 +/- 3.8 mg/kg/day in control children) was significantly higher than in controls whereas bile acid synthesis was similar in both groups. Absorption of orally administered [1,2-3H]cholesterol was lower in the abetalipoproteinemic subjects than the controls and subsequent labeling of plasma cholesterol in the former patients was minimal (less than 3% of controls). The mechanisms for the increased sterol synthesis in abetalipoproteinemia may relate to the absence of chylomicrons and low density lipoproteins in plasma, but the magnitude of the increase can be largely explained on the basis of enhanced sterol losses that occur secondary to malabsorption of biliary cholesterol.