The effects of long term treatment with nicotinic acid on lipids, lipoproteins, and the plasma distribution of very low density lipoproteins (VLDL) apoprotein C (ApoC) subspecies were studied in 33 patients with types IIa (n = 9), IIb (n = 11), and IV (n = 13) hyperlipidemias. After 6 months of treatment, a significant decrease in triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol levels occurred. High density lipoprotein (HDL) cholesterol increased significantly by 31.1%, 41.8%, and 32.0% in types IIa, IIb, and IV, respectively (P less than 0.01 for all). A significant negative correlation existed between changes in HDL cholesterol and triglycerides (r = -0.613; P less than 0.02) in all groups studied. Therapy also produced changes in VLDL, LDL, and HDL protein concentrations. VLDL protein decreased from 20.9 +/- 3.9 to 15.2 +/- 1.0 mg/dl (P less than 0.05) in type IIa. In types IIb and IV, mean VLDL protein decreased from 44.7 +/- 8.2 to 27.1 +/- 3.9 mg/dl (P less than 0.001) and from 46.3 +/- 7.1 to 30.6 +/- 4.9 mg/dl (P less than 0.001), respectively. LDL protein decreased significantly, and HDL protein increased in type IIa only. Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies. This resulted in increases in the ApoC-II to ApoC-III area ratio from 0.50 +/- 0.1 to 1.02 +/- 0.2 (P less than 0.001) in type IIb and from 0.62 +/- 0.07 to 0.88 +/- 0.13 (P less than 0.01) in type IV, respectively. The ApoE subspecies and the ApoE-III to ApoE-II area ratio did not change significantly. Our results show that nicotinic acid produces a significant improvement in the lipoprotein profiles of these patients.