The turnover and metabolism of the individual C apolipoproteins (C-II, C-III1, and C-III2) were studied following the injection of 125I-labeled VLDL into 15 normal and hyperlipoproteinemic subjects. The C apolipoproteins from very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were separated by analytical isoelectric focusing, and subsequent densitometric scanning and radioassay of the stained bands yielded values for specific activity. In 13 of 15 subjects, kinetics of C-II, C-III1, and C-III2 were best described by a one-pool model, whereas two subjects showed biexponential kinetics. The specific activity-time curves for VLDL and HDL were super-imposable, indicating rapid exchange of all C apolipoproteins in hyperlipidemic as well as in normal subjects. In each subject the half-life was similar for C-II, C-III1, and C-III2, which suggests similar synthesis and catabolic mechanisms for each C apolipoprotein. The mass of exchangeable C-II (range 1.0-5.8 mg/kg), C-III1 (2.6-20 mg/kg), and C-III2 (2.0-13 mg/kg) increased with plasma triglyceride concentrations. Values for flux of C-II were 1.0-2.8 mg/d per kg, for C-III1 1.6-5.6 mg/d per kg, and for C-III2 1.2-3.1 mg/d per kg, but they were not related to levels of plasma triglyceride. However the irreversible fractional catabolic rates were inversely related to C apolipoprotein (and triglyceride) mass, suggesting that expansion in C apolipoprotein pool size is related to slower removal, due to the longer residence time of triglyceride-rich VLDL particles in plasma. This was confirmed by similar findings for B apolipoprotein kinetics in VLDL carried out simultaneously.