The glycemic and hormonal responses to protein, fat and carbohydrate alone and together were studied in normal, noninsulin-dependent (NIDD) and insulin-dependent (IDD) diabetic subjects. Fat and protein markedly reduced the glycemic response to oral carbohydrate in nondiabetics. In NIDD, the presence of protein and fat had no significant effect on the glycemic response. In IDD, while fat had no effect, protein enhanced the glycemic response. The insulin and GIP responses to the macronutrients together and individually were remarkably similar in all subject groups. Protein behaved as an insulin secretagogue in normal and NIDD while fat acted as a GIP secretagogue in normal and both diabetic groups. Protein appeared to function as a GIP secretagogue when combined with both fat and carbohydrate. It is concluded that caution is required when the glycemic responses to foods observed in nondiabetics are extended to diabetics.