To further understand the effect of high carbohydrate (CHO)-low fat diets and the role of variations in dietary sucrose on CHO and lipid metabolism, 10 patients with hypertriglyceridemia were fed 2 isocaloric, typical American diets, containing 40% and 60% CHO, for 15 days in random sequence. Each patient was their own control, and they were divided into 2 groups of 5 patients each. In one group, sucrose was held constant at 13% of total calories (40-13% and 60-13%), whereas the sucrose content was 9% of the total calories on a 40% CHO diet (40-9%), and 15% of total calories on a 60% CHO diet (60-15%) in the other group. Fasting and postprandial blood samples were analyzed for plasma glucose, insulin, cholesterol (Chol), and triglycerides (TG), as well as for Chol and TG in chylomicrons, very low density, low density, and high density lipoproteins (HDL). Fasting plasma TG levels were significantly increased in both groups on the 60% CHO diet, primarily due to increases in very low density-TG concentration. The magnitude of the elevation was attenuated when sucrose content was kept constant. Postprandial TG responses were qualitatively similar. There were no significant changes in plasma Chol concentrations, except for a modest fall in plasma HDL-Chol level after the 60-13% diet period (P less than 0.05). No significant differences were found in fasting plasma glucose or insulin concentration. However, postprandial glucose and insulin responses were increased on both high CHO diets. The results of these studies demonstrate that high CHO-low fat diets, in general, tend to elevate plasma glucose, insulin, and TG concentrations and reduce HDL-Chol concentration in patients with endogenous hypertriglyceridemia. In addition, these data illustrate the important role that small variations in dietary sucrose can play in modulation of CHO and lipid metabolism.