Immunoreactive insulin (IRI) response to successive i.v. injections of glucose (0.3 g/kg), arginine (5 g) and tolbutamide (20 mg/kg) was measured in 11 non-obese patients with mild glucose intolerance and 11 control subjects. In 3 of the patients the IRI response to i.v. arginine and subsequent i.v. glucose was also measured. The mean peak IRI level following glucose was grossly diminished in the patients compared to controls but peak IRI levels following arginine and tolbutamide were similar in the two groups. Administering arginine prior to glucose in the 3 patients tested resulted in a lowering of the IRI response to arginine but no increase in the IRI response to glucose. The decreased IRI response to i.v. glucose associated with an adequate response to i.v. arginine and tolbutamide in these patients suggests a failure of the B-cell sensor mechanism for glucose and may provide a physiological explanation for the recognized value of restricting carbohydrate relative to protein in the treatment of this condition. Any defect in the sensor mechanism for arginine appears quantitatively much less severe than that to glucose.