The Zucker (fatty) rat is one of a group of animals that inherit obesity as an autosomal Mendelian recessive trait. These rats are obese, hyperphagic, and hyperinsulinemic, but blood glucose remains at normal levels. Although these rats eat more than normal rats, their response to the addition of adulterants to the food or after exposure to the cold is more like that of normal rats than rats with hypothalamic obesity. The hypertriglyceridemia which characterized these animals is due to the increased hepatic production of a very low density lipoproteins. Adipocytes are increased in size and in number with the subcutaneous fat depot showing the largest increase in the number of fat cells. Lipogenesis from glucose is brisk in the young animals but declines with age. Enzymatic patterns of glycolysis and gluconeogenesis appear to reflect the altered internal milieu rather than specific defects. Endocrine changes in the fatty rat include hyperinsulinemia, reduced levels of glucagon, hypothyroidis, and impaired reproductive function. A model is presented in which the features of the genetically obese (Zucker) fatty rat are compared with those of animals with hypothalamic obesity.