To test the hypothesis that nocturnal hypoglycemia causes fasting hyperglycemia (the Somogyi phenomenon) in patients with insulin-dependent diabetes mellitus, we studied 10 patients, who were on their usual therapeutic regimens, from 10 p.m. through 8 a.m. on three nights. On the first night, only a control procedure was performed (blood sampling only); on the second night, hypoglycemia was prevented (by intravenous glucose infusion, if necessary, to keep plasma glucose levels above 100 mg per deciliter [5.6 mmol per liter]); and on the third night, hypoglycemia was induced (by stepped intravenous insulin infusions between midnight and 4 a.m. to keep plasma glucose levels below 50 mg per deciliter [2.8 mmol per liter]). After nocturnal hypoglycemia was induced (36±2 mg per deciliter [2.0±0.1 mmol per liter] [mean ±SE] from 2 to 4:30 a.m.), 8 a.m. plasma glucose concentrations (113±18 mg per deciliter [6.3±1.0 mmol per liter]) were not higher than values obtained after hypoglycemia was prevented (182±14 mg per deciliter [10.1 ±0.8 mmol per liter]) or those obtained after blood sampling only (149±20 mg per deciliter [8.3±1.1 mmol per liter]). Indeed, regression analysis of data obtained on the control night indicated that the 8 a.m. plasma glucose concentration was directly related to the nocturnal glucose nadir (r = 0.761, P = 0.011). None of the patients was awakened by hypoglycemia. Scores for symptoms of hypoglycemia, which were determined at 8 a.m., did not differ significantly among the three studies. We conclude that asymptomatic nocturnal hypoglycemia does not appear to cause clinically important fasting hyperglycemia in patients with insulin-dependent diabetes mellitus on their usual therapeutic regimens. (N Engl J Med 1987; 317:1552–9.) IN 1938, at a meeting of the St. Louis Medical Society, Dr. Michael Somogyi1 stated: [W]e obtained evidence to the effect, that the extreme fluctuations in the blood sugar level, and the progressively increasing unstability of diabetic patients, are the direct results of the administration of excessive amounts of insulin…. In the past we failed to recognize the cause and effect relationship between hypoglycemia and hyperglycemia, and by administering insulin doses sufficiently large to cause hypoglycemias, we produced more severe hyperglycemias. This concept, which has become known as the Somogyi phenomenon, was based on the finding.