The 12-hr profiles of plasma glucose and insulin concentrations in 26 normal subjects ingesting a diet high in carbohydrate, protein, or fat have been determined. The diets were isocaloric and were given as three identical meals 4 hrs apart. In males the high carbohydrate diet resulted in glucose profiles similar to those obtained with the standard diet. In females the peak glucose concentration also was not increased but the glucose concentration remained elevated longer after each meal. In both groups the insulin curves followed the glucose curves. The post-meal glucose and insulin areas were significantly increased in the female group. The high protein diet resulted in only a small post-meal glucose rise particularly later in the day in both males and females. However, there was a sharp rise in insulin concentration after each meal. The total insulin area after each meal was nearly as great as with the standard diet. The high fat diet, which contained approximately the same carbohydrate content as the high protein diet, induced a clear increase in glucose concentration after each meal in the female group. However, the peak was progressively delayed with each meal. The insulin curves followed the glucose curves. In males a small, prolonged post-meal increase in glucose was observed after each meal. The insulin concentration increased modestly after the first meal and then remained elevated and changed little after the subsequent meals. These data help to define the glucose and insulin responses to meals varying greatly in protein, carbohydrate, and fat content and further indicate the need to consider the response of males and females separately.