To examine the effects of dietary fatty acids and carbohydrate on plasma lipids and lipoproteins, 11 patients with a mean plasma total cholesterol level of 251 +/- 10 mg per deciliter were studied on a metabolic ward during three dietary periods, each lasting four weeks. A liquid diet rich in monounsaturated fatty acids ("High-Mono") and a diet low in fat ("Low-Fat") were compared with a diet high in saturated fatty acids ("High-Sat"). The High-Sat and High-Mono diets contained 40 percent of their total calories as fat and 43 percent as carbohydrate; the Low-Fat diet had 20 percent fat and 63 percent carbohydrate. Body weight was kept constant by adjusting total caloric intake. As compared with the High-Sat diet, both the High-Mono and Low-Fat diets lowered plasma total cholesterol (by 13 percent and 8 percent, respectively) and low-density lipoprotein cholesterol (by 21 percent and 15 percent, respectively). As compared with the High-Sat diet, the Low-Fat diet raised triglyceride levels and significantly reduced plasma high-density lipoprotein cholesterol. In contrast, the High-Mono diet had no effect on levels of triglycerides or high-density lipoprotein cholesterol. The ratio of low-density to high-density lipoprotein cholesterol was also significantly lower when the High-Mono diet rather than the Low-Fat diet was followed. Therefore, in short-term studies in which liquid diets are used and body weight is kept constant, a diet rich in monounsaturated fatty acids appears to be at least as effective in lowering plasma cholesterol as a diet low in fat and high in carbohydrate.