Information on the metabolic response in people with non-insulin-dependent diabetes mellitus (NIDDM) to ingested individual macronutrients is limited. Available information is reviewed herein. The major absorbed products of carbohydrate-containing foods are glucose, fructose, and galactose. The quantitative effect of these on the plasma glucose and insulin response is different for each. In addition, available data indicate that the glucose and particularly the insulin response is different from that in nondiabetic people. The quantitative effect of dietary proteins and fats on the circulating glucose and insulin concentrations in nondiabetic and NIDDM subjects also has been reviewed. Neither has a significant effect on the glucose concentration. Protein stimulates insulin secretion, and this is relatively more prominent in people with NIDDM. A strong synergistic interaction with glucose on insulin secretion is present, but this is absent in nondiabetic people. Ingested fat does not independently stimulate insulin secretion. However, when ingested with carbohydrate, it may have a considerable effect on the plasma glucose and/or insulin response to that carbohydrate, and the responses are different in nondiabetic and NIDDM subjects. This is probably not due to altered carbohydrate absorption. Intestinal hormones undoubtedly are playing a large role in the insulin secretory response in all of these studies, but this remains to be completely elucidated. Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people. In our opinion, much more information is required before dietary recommendations for NIDDM subjects can be made based on solid scientific data.