Previous studies have shown that supplementation of the diet with oat bran may lower serum cholesterol levels. However, it is not known whether oat-bran diets lower serum cholesterol levels by replacing fatty foods in the diet or by a direct effect of the dietary fiber contained in oat bran. To determine which is the case, we compared the effect of isocaloric supplements of high-fiber oat bran (87 g per day) and a low-fiber refined-wheat product on the serum lipoprotein cholesterol levels of 20 healthy subjects, 23 to 49 years old. After a one-week base-line period during which they consumed their usual diets, the subjects were given each type of supplement for six-week periods in a double-blind, crossover trial. Mean serum cholesterol levels (+/- SD) were not significantly different during the high-fiber and low-fiber periods: total cholesterol, 4.44 +/- 0.73 and 4.46 +/- 0.64 mmol per liter (172 +/- 28 and 172 +/- 25 mg per deciliter); low-density lipoprotein, 2.69 +/- 0.63 and 2.77 +/- 0.59 mmol per liter (104 +/- 24 and 107 +/- 23 mg per deciliter); and high-density lipoprotein, 1.40 +/- 0.39 and 1.32 +/- 0.39 mmol per liter (54.2 +/- 15.0 and 50.9 +/- 15.2 mg per deciliter), respectively. However, both types of supplements lowered the mean base-line serum cholesterol level, 4.80 +/- 0.80 mmol per liter (186 +/- 31 mg per deciliter), by 7 to 8 percent (95 percent confidence interval for high fiber, 11 to 4 percent, and for low fiber, 11 to 3 percent). The subjects ate less saturated fat and cholesterol and more polyunsaturated fat during both periods of supplementation than at base line. Those changes in dietary fats were sufficient to explain all of the reduction in serum cholesterol levels caused by the high-fiber and low-fiber diets. The average blood pressure was 112/68 mm Hg at base line and did not change during either dietary period. We conclude that oat bran has little cholesterol-lowering effect and that high-fiber and low-fiber dietary grain supplements reduce serum cholesterol levels about equally, probably because they replace dietary fats.