The effect of psyllium hydrophilic mucilloid on serum cholesterol levels was investigated in 26 men with mild to moderate hypercholesterolemia (range of cholesterol level, 4.86 to 8.12 mmol/L [188 to 314 mg/dL]) in a double-blind, placebo-controlled parallel study. Following a two-week baseline period, subjects were treated for eight weeks with 3.4 g of psyllium or cellulose placebo at mealtimes (three doses per day). All subjects maintained their usual diets, which provided less than 300 mg of cholesterol per day and approximately 20% of energy from protein, 40% from carbohydrate, and 40% from fat. Eight weeks of treatment with psyllium reduced serum total cholesterol levels by 14.8%, low-density lipoprotein (LDL) cholesterol by 20.2%, and the ratio of LDL cholesterol to high-density lipoprotein cholesterol by 14.8% relative to baseline values. The reductions in total cholesterol and LDL cholesterol became progressively larger with time, and this trend appeared to be continuing at the eighth week. Psyllium treatment did not affect body weight, blood pressure, or serum levels of high-density lipoprotein cholesterol, triglycerides, glucose, iron, or zinc. No significant changes in serum lipid levels, body weight, blood pressure, or other serum parameters were observed with placebo treatment. Subject adherence to psyllium treatment was excellent, and no adverse effects were observed. Results of this study show that psyllium is an effective and well-tolerated therapy for mild to moderate hypercholesterolemia.