To determine if dietary fructose causes adverse metabolic effects, we used a crossover design to compare a diet containing 20% of energy from fructose with an isoenergic high-starch diet that contained less than 3% fructose. Fourteen healthy subjects consumed each diet for 28 d. There were no significant differences between the diets in the mean values of hemoglobin A1C, serum glycosylated albumin, fasting plasma glucose, peak postprandial plasma glucose, integrated plasma glucose, fasting serum lactate, or fasting serum triglycerides. Peak postprandial serum lactate was significantly higher during the fructose diet at days 1, 7, and 14 but not at days 21 or 28. Peak postprandial serum triglycerides were significantly higher only at day 1 of the fructose diet. Day-28 fasting serum total and LDL cholesterol for the fructose diet were 9.0% and 11.0% higher, respectively, than the corresponding values for the starch diet. A high-fructose diet compared with a high-starch diet resulted in significantly higher fasting serum total and LDL cholesterol and also caused transient changes in postprandial serum lactate and triglycerides.