We have previously demonstrated that while VLDL-TG production increased in subjects fed high CHO diets, VLDL apo-B production did not change. To further define the effects of high CHO diets on apo-B metabolism in man, we studied the catabolism of this apoprotein in VLDL, IDL, and LDL in three hypertriglyceridemic subjects during control and high CHO diets. ¹²⁵I-VLDL was injected intravenously into subjects and 18 blood samples obtained over the following 48-hr period. VLDL, IDL, and LDL were isolated by sequential ultracentrifugation at each time point and the specific radioactivity of apo-B in each lipoprotein class was determined. A multicompartmental analysis was utilized to analyze the three radioactivity curves obtained in each study. The major change in apo-B catabolism during the high CHO diet involved the conversion of VLDL apo-B to LDL apo-B. During the control diet, 40%–62% of VLDL apo-B was converted to LDL apo-B while during the high CHO period, only 16%–42% of VLDL apo-B was converted to LDL. The reduction in conversion resulted from two separate processes. First, direct catabolism of VLDL apo-B without conversion to higher density lipoprotein classes increased during the high CHO diet. Second, although during the control period approximately 25% of VLDL apo-B was converted directly to LDL apo-B (without passing through the IDL density range), essentially no VLDL apo-B degradation occurred via this route during the high CHO period. Thus, although the rate of VLDL apo-B secretion into plasma was the same during both diet periods, significant alterations in the routes of catabolism of apo-B occurred on the high CHO diet.