Turnover kinetics of triglycerides (TG) and apolipoprotein-B (apo-B) of plasma very low density lipoprotein (VLDL) and their relationship to plasma VLDL composition and VLDL apo-B conversion to low density lipoprotein (LDL) were determined in age and weight-matched groups of normolipemic (NL) healthy subjects, patients with familial combined hyperlipidemia (FCHL) and patients with familial hypertriglyceridemia (FHTG). In NL subjects, a significant correlation as observed between VLDL TG or VLDL apo-B turnover rate and its circulating mass, suggesting that the plasma level of VLDL was determined by the secretion rate of VLDL TG and apo-B. The positive significant correlation between VLDL TG and apo-B also suggests that the production of these moieties was integrated at the synthetic and/or secretory sites to maintain the ratio of TG to apo-B in plasma VLDL. In moderately obese NL subjects, proportionate increases in VLDL TG and apo-B turnover rates resulted in enhanced secretion of VLDL particles. Both groups with genetic hypertriglyceridemia had increased VLDL TG and VLDL apo-B turnover rates. This increase accounted for the increase in circulating VLDL TG and apo-B mass. In patients with FCHL, turnover rates of VLDL TG and apo-B were equally increased, hence, the ratios between major VLDL constituents were within normal limits. On the other hand, the increase in VLDL TG turnover in patients with FHTG was disproportionately greater than that of apo-B resulting in a higher ratio of TG to other VLDL components. In NL subjects, approximately 72% of VLDL apo-B released into plasma was converted to LDL. This conversion correlated positively with VLDL apo-B turnover rate and inversely with VLDL TG turnover rate. Formation of LDL from VLDL was significantly greater in the obese individuals. In FCHL, conversion of VLDL to LDL represented the major pathway for VLDL apo-B catabolism. The increased VLDL apo-B load was predominantly catabolized to LDL. The greater increase in VLDL TG turnover relative to apo-B in FHTG, on the other hand, resulted in a smaller fraction of VLDL apo-B recovered in LDL, most of the VLDL apo-B being removed via a pathway that did not involve this conversion. We conclude that the composition and metabolic fate of plasma VLDL may be greatly influenced by the secretion rates of VLDL TG and apo-B. If VLDL conversion to LDL and the subsequent catabolism of the latter provides a major route for delivery of cholesterol ester to peripheral tissues, then the increased LDL production in FCHL compared to FHTG may account for a higher cardiovascular risk.