The purpose of this study was to confirm and extend previous findings that serum cholesterol response to a fat-modified diet is enhanced by oat fiber. Participants (n = 236) were recruited from the Continental Illinois National Bank in Chicago. Data including weight, serum lipid level, lipoproteins, and 3-day food records were collected at baseline and every 4 weeks for 12 weeks. All participants were instructed to follow the fat-modified (Phase II) diet recommended by the American Heart Association (AHA). After 4 weeks, participants were randomly assigned to one of two groups. While both groups continued to follow the AHA diet, Group 1 was instructed to include 2 oz (56 g, dry wt) of oatmeal, isocalorically substituted for other carbohydrate foods. Group 2 served as the control and consumed no oat products throughout the study. Serum cholesterol values at baseline and after 4 weeks of the AHA diet were similar for both groups (203.9 and 193.0 mg/dl for Group 1 and 205.3 and 194.5 mg/dl for Group 2). After 4 weeks of oatmeal intervention, mean group differences were -6.8 and -2.1 mg/dl (P = 0.008 one-tailed t test) for Groups 1 and 2, respectively. Following an additional 4 weeks of oatmeal intervention, the Group 1 mean cholesterol increased slightly (0.9 mg/dl), while the Group 2 level decreased slightly (-0.7 mg/dl). Overall serum cholesterol responses for the two groups from Visit 2 to Visit 4 were -6.0 and -2.8 mg/dl for Groups 1 and 2, respectively (P = 0.074, one tail). Changes in weight were small and nonsignificant. Subgroup analyses revealed greater reductions in serum cholesterol among participants with the highest baseline serum cholesterol (-8.0 mg/dl vs -1.7 mg/dl for Subgroups 1 and 2, respectively). These data support previous findings that inclusion of oatmeal in a fat-modified diet is helpful in lowering serum cholesterol, particularly for individuals with elevated serum cholesterol levels.