The Low Glycemic Index and Cholesterol study was a 12-week randomized clinical trial comparing the effects on serum lipids of a novel low-fat/low-glycemic index (GI) diet with those of a low-fat only diet in adults with hypercholesterolemia. Sixty-two subjects (men and women) with elevated serum low-density lipoprotein cholesterol were randomized to one of the two dietary interventions. The low-GI intervention included substituting low-GI carbohydrates for high-GI carbohydrates. Dietary assessment and serum lipid measurements were performed at baseline (BL), 4 weeks (FV4), and 12 weeks (FV12). In the low-fat/low-GI group, dietary GI and glycemic load significantly decreased between the BL and FV4 and BL and FV12 time intervals; however, there were no significant differences in lipid values between the two groups at any time point. Importantly, whereas high-density lipoprotein cholesterol was unchanged in the low-fat/low-GI group over the 12 weeks, it decreased 5 mg/dL (11.4%) in the low-fat only group (P = .05). © 2005 Elsevier Inc. All rights reserved.