We have studied the effects of moderate dietary fat restriction on plasma triglyceride, cholesterol, glucose, and insulin response in 27 subjects. Compared with a control diet (45% fat, 40% carbohydrate [CHO], 15% protein) the low fat (higher CHO) diet (30% fat, 55% CHO, 15% protein) produced a 41% increase in fasting triglyceride level (155 +/- 17 to 219 +/- 23 mg%) with no change in fasting plasma cholesterol level. Furthermore, this increase in triglyceride levels; induced by the higher CHO content of the low fat diet, was seen in 26 out of 27 subjects. Postprandial triglyceride, glucose, and insulin levels were also higher on the low fat (higher CHO) diet. Since hypertriglyceridemia is a significant risk factor for the development of coronary heart disease, and since our data indicate that the moderate increase in dietary CHO associated with a low fat diet will elevate plasma triglyceride levels, we believe that more caution is necessary before recommending the wide-spread use of low fat diets for heart disease prevention.