Increased intestinal viscosity appears to be the major mode of action by which dietary oat beta-glucan increases the fecal excretion of bile acids and thereby lowers blood cholesterol concentrations. The objective of this experiment was to investigate whether there is a difference in effects on blood lipids between two yeast-leavened oat bran breads containing beta-glucan (6 g/d) of low or high average molecular weight (HMW) (217 or 797 kDa, respectively). The breads were fed to 22 volunteers (women, n = 11; men, n = 11) in a randomized, double-blind, crossover design. The participants ate one bread for 3 wk as part of their normal diet and switched breads after a 2-wk washout period. Blood samples were drawn from fasting subjects and analyzed for lipids, insulin, glucose, and alpha- and gamma-tocopherol. The two experimental oat breads did not differ in their effects on any of the variables measured. Compared to baseline, however, consumption of HMW bread increased serum insulin by 22.6% (P < 0.03) and decreased blood glucose concentrations by 3.4% (P < 0.05). These results suggest that the molecular weight, when beta-glucan is consumed in oat bran breads as part of the habitual diet, does not play an important physiological role in moderately hypercholesterolemic humans.