We have developed radioimmunoassays for the quantification of apolipoproteins (apo) C-I, C-II, and C-III in human plasma. The apo C proteins were isolated from very low-density lipoproteins of patients with hypertriglyceridemia, fractionated on a Sephacryl column, and purified by diethylaminoethyl cellulose anion-exchange chromatography followed by reverse-phase fast protein liquid chromatography. The assays were sensitive, specific, and reproducible, and the standards demonstrated parallel immunoreactivity with plasma samples. Patients with hypertriglyceridemia (triglyceride level more than 2,200 mg/liter)--14 patients with diabetes and 12 with type V hyperlipoproteinemia--were compared with age- and sex-matched control subjects. In comparison with the control groups, levels of apoproteins C-I, C-II, and C-III were significantly increased in both disease groups, but the ratios of the C peptides to triglycerides were significantly lower, an indication of a relative deficiency of C apoproteins in hypertriglyceridemic states. Independent radioimmunoassays for each of the C apolipoproteins would help to study their individual roles in triglyceride-rich lipoprotein metabolism.