Eight patients are presented in whom obesity developed in association with documented hypothalamic lesions. These lesions included trauma, inflammatory disease, an aneurysm of the internal carotid artery, and five cases of tumor. Detailed metabolic studies were performed in four patients with hypothalamic obesity and in five age- and weight-matched patients with essential obesity(i.e., obesity with no definable etiology). Fasting insulin concentrations were significantly higher in the patients with hypothalamic obesity. During a seven-day fast the insulin levels in patients with essential obesity decreased by 24 to 48 hours, whereas patients with hypothalamic obesity showed a variety of changes; In three out of four of these patients with hypothalamic obesity there was no evidence for hyperplasia of the fat cells. Basal oxygen consumption, body composition, and metabolism of adipose tissue did not differ between the patients with essential obesity and those with hypothalamic obesity. There was no difference in activity of the enzymes in the glycerophosphate cycle. Our data on eight patients with hypothalamic obesity were compared with data on patients in literature. Most cases of hypothalamic obesity occur with space-occupying tumors arising at the base of the hypothalamus. However, trauma, inflammatory diseases, and leukemia are also associated with hypothalamic obesity. Patients with hypothalamic obesity rarely weigh more than 140 kg.