To clarify the impairment of carbohydrate metabolism in hyperthyroidism, we performed the oral glucose tolerance test (OGTT) and glucagon tolerance test in ten patients with hyperthyroidism due to Graves' disease (GD) and in ten normal subjects. During OGTT, glucose and insulin values in the GD patients were twice as high as those in the normals. The ratio of cumulative net plasma glucose [sigma PG (0-120 minutes)] and insulin [sigma IRI (0-120 minutes)] was 0.83 +/- 0.14 and 1.14 +/- 0.25 in the GD patients and normals, respectively. During the glucagon tolerance test, plasma glucose showed lower peaks in the GD patients than in the normals. C-peptide reached a peak value at 6 min in the GD patients and at 10 min in the normals. Cyclic AMP response in the GD patients was three times greater than that in the normals. A smaller insulinogenic index and a smaller sigma PG/sigma IRI ratio in the GD patients suggest that the secretion of insulin in GD patients does not meet the demand despite the higher insulin values observed during OGTT. Greater response of cAMP, smaller and earlier peaks of C-peptide and smaller response of glucose to glucagon in the GD patients may suggest a rapid insulin turnover and a reduction of glycogen storage in the liver with hyperthyroidism.