When normal volunteers ate isocaloric wheat-based meals, their plasma insulin responses (peak concentration and area under curve) increased stepwise: whole grains less than cracked grains less than coarse flour less than fine flour. Insulin responses were also greater with fine maizemeal than with whole or cracked maize grains but were similar with whole groats, rolled oats, and fine oatmeal. The peak-to-nadir swing of plasma glucose was greater with wheat flour than with cracked or whole grains. In vitro starch hydrolysis by pancreatic amylase was faster with decreasing particle size with all three cereals. Correlation with the in vivo data was imperfect. Oat-based meals evoked smaller glucose and insulin responses than wheat- or maize-based meals. Particle size influences the digestion rate and consequent metabolic effects of wheat and maize but not oats. The increased insulin response to finely ground flour may be relevant to the etiology of diseases associated with hyperinsulinemia and to the management of diabetes.