Neuropathological studies of Huntington’s disease reveal neuronal atrophy, lipofuscin accumulation and other findings characteristic of the aged brain, although the onset of disease is only the fourth decade. The pathology is limited to specific areas such as the caudate nucleus, cerebral cortex and hypothalamus. 14 patients with documented Huntington’s disease (mean age of 44.4 years with a range of 27–79 years) were studied by oral glucose tolerance tests (GTT) and intravenous arginine tolerance tests performed under standardized metabolic conditions. Seven of the 14 patients had impaired carbohydrate tolerance. Mean plasma glucose level at 2 h was 90.4 ± 6.2 mg/l00 ml in the patients with a normal GTT and 148.1 ± 8.9 mg/l00 ml in the patients with a diabetic type GTT. Mean peak insulin level in the nondiabetic group occurred at 1/2 h and was 60.2 ± 10.1 μ U/ml, but in the diabetic group the peak insulin level occurred at 2h and was 155.9 ± 33.8 μU/ ml. There was failure of suppression of growth hormone during the GTT, with a rise to abnormally high levels at 5 h (18.6 ± 5.6 ng/ml). Arginine infusion resulted in normal glucose and insulin rise in the nondiabetic patients with Huntington’s disease. However, arginine infusion provoked an elevated insulin response in those with a diabetic GTT, and an exaggerated growth hormone response in the majority of the patients. It is uncertain whether these observations are related to abnormal cerebral aging per se, direct hypothalamic neuronal degeneration, or perhaps a relative imbalance of intracerebral neurotransmitters incl