Plasma lipid and apolipoprotein (apo) levels were determined in five normolipidemic subjects and five patients with Type IV hypertriglyceridemia (HTG) who were fed for greater than or equal to 6 weeks on two isocaloric diets. The first diet contained carbohydrates (CHO) as 55% of total calories, 29% as fat and 16% as protein. The second diet contained 40% CHO, 45% fat and 15% protein in normolipidemic subjects and 40% CHO, 41% fat and 19% protein in patients with HTG. All diets had a cholesterol content of approximately 400 mg/day and a polyunsaturated/saturated fatty acid ratio of approximately 1:0. Apo A-1 kinetics were measured during the last 2 weeks of each dietary period. The composition and distribution of high-density lipoproteins (HDL), subclasses HDL2 and HDL3, were determined at the end of each dietary term. In the HTG patients, administration of a 40% compared with 55% CHO diet caused a significant decrease of plasma triglyceride levels and an increase of HDL-cholesterol; low-density lipoprotein (LDL) levels increased and very low-density lipoprotein (VLDL) levels decreased (P less than 0.01 and less than 0.07, respectively). Similar quantitative changes of VLDL and HDL levels were found in the normolipidemic subjects. No significant change in plasma levels of apo A-I, A-II and E occurred. Apo A-I kinetic studies revealed decreased synthetic rates and fractional catabolic rates on the low CHO diet. Separation of HDL subfractions by zonal ultracentrifugation in both groups revealed an increase in HDL3-cholesterol ester and protein, and a decrease in HDL2 protein, phospholipid and cholesterol. Our findings indicate that moderate changes in dietary CHO and fat content affect HDL levels, composition and apo A-I metabolism.