A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus.