An analysis of apolipoprotein (apo) B turnovers conducted in subjects with moderate hypercholesterolemia was performed to discover relationships that may exist between apoB kinetic parameters and plasma lipid and lipoprotein levels. A group of 21 subjects with plasma cholesterol in the range 250-300 mg/dl and triglyceride < 265 mg/dl were injected with tracers of 131I-labeled very low density lipoprotein 1 (VLDL1, Sf 60-400) and 125I-labeled VLDL2 (Sf 20-60) prepared by cumulative flotation ultracentrifugation. The metabolism of apoB in these fractions was followed through intermediate density (IDL, Sf 12-20) to low density (LDL, Sf 0-12) lipoprotein. The most consistent feature giving rise to the higher apoB levels that occurred in VLDL2, IDL, and LDL in the hypercholesterolemic group was increased input of VLDL2 (787 +/- 607 (SD) mg/day vs. 349 +/- 213 in normals, P < 0.01). VLDL1 apoB input was variably affected and not significantly different from normal. However, the plasma residence time of this subfraction was increased (0.15 +/- 0.07 days vs. 0.08 +/- 0.03 days in normals, (P < 0.001) due to a decreased fractional rate of direct catabolism. Fractional transfer rates (FTR) down the delipidation cascade and other fractional rates of direct catabolism were, overall, not significantly different from normal. The plasma residence time of VLDL2 apoB and LDL apoB was similar in hypercholesterolemic and normal subjects, while that of IDL apoB was slightly increased. Variation in LDL apoB mass within the hypercholesterolemic group correlated with VLDL1 apoB input (r = 0.58, P = 0.006), the fractional rate of transfer from IDL to LDL (r = 0.61, P = 0.003), and direct LDL input (r = 0.64, P = 0.002). The proportion of LDL apoB mass derived by direct, i.e., VLDL-independent input, varied from 5 to 50% and was inversely correlated with plasma triglyceride (r = -0.53, P = 0.014) and positively with HDL2 (r = 0.66, P = 0.002). In addition, the amount of direct LDL input was related to the amount of VLDL1 removed by direct catabolism (r = 0.53, P = 0.013). The analysis indicated that moderate hypercholesterolemia arose principally from overproduction of small VLDL, while variation in VLDL1 input and the IDL to LDL conversion rate (presumably hepatic lipase-mediated) modulated the extent of the elevation in LDL apoB.