The controversial question of the relationship between obesity and disease has been considerably clearer after the demonstration in several prospective, epidemiological studies that the subgroup of central, visceral obesity is particularly prone to develop cardiovascular disease, stroke, and non-insulin dependent diabetes mellitus. Visceral obesity is associated with multiple central endocrine aberrations. The hypothalamo-adrenal axis is apparently sensitive to stimuli, sex steroid hormone secretion blunted, and hyperandrogenicity is found in women. In addition, there seem to be signs of central dysfunctions in the regulation of hemodynamic factors after stress, and growth hormone secretion appears to be particularly blunted. Several of these endocrine abnormalities are associated with insulin resistance, particularly glycogen synthesis in muscle. Fiber composition with low type I/type II ratio might be secondary to the prevailing hyperinsulinemia, but low capillary density in muscle may well be of importance. In combination with elevated turn-over of free fatty acids (FFA) this will probably provide powerful mechanisms whereby insulin resistance is created. Portal FFA, from the highly lipolytic visceral depots may, in addition, affect hepatic metabolism to induce increased gluconeogenesis, production of very low density lipoproteins as well as to perhaps inhibit clearance of insulin. By these mechanisms a Metabolic Syndrome Visceral adipocytes seem to have a high density of several steroid hormone receptors, directing steroid hormone effects particularly to these depots. The net effect of cortisol is apparently a stimulation of lipid storage, with opposing effects of sex steroid hormones which also facilitate lipid mobilization, regulations most often found at the gene transcription level. Growth hormone inhibits cortisol effects on lipid accumulation, and amplifies the lipid mobilizing effects of steroid hormones. The combined perturbations of hormonal secretions will therefore probably direct triglycerides toward visceral depots. Circulatory and nervous regulatory mechanisms require, however, more attention. The multiple central endocrine and nervous aberrations of visceral obesity suggest neuroendocrine dysregulations, and have features characteristic of the hypothalamic arousal seen after certain types of stress, alcohol intake, and smoking. Such factors can be traced to subjects with visceral fat accumulation. Standardized stress, eliciting a "defeat reaction" in primates is followed by an apparently identical syndrome. This integrated picture of the multiple symptoms of visceral obesity is based on epidemiological, clinical, experimental, cellular, and molecular evidence. The ingredients of positive energy balance, including physical inactivity, stress, smoking, and alcohol consumption are frequent features of modern, urbanized society. Visceral obesity may therefore be an expression of a "Civilization Syndrome."