Enzymatic changes associated with development of obesity were examined on two types of genetically obese animals, fatty rats and yellow KK mice. Fatty rats showed higher levels of lipogenic enzymes (6- phosphogluconate dehydrogenase, acetyl-CoA carboxylase, ATP citrate lyase and malic enzyme) in adipose tissue as compared with their lean littermates. In liver of fatty rats, increased activities were observed in the above lipogenic enzymes, glycolytic enzymes (glucokinase and pyruvate kinase), and gluconeogenic enzymes (glucose-6-phosphatase and fructose- 1,6-diphosphatase). Yellow KK mice with obesity and severe diabetes showed higher levels of hepatic enzymes in glycolysis, gluconeogenesis and lipogenesis when compared with control KK mice (Taketomi, Tsuda, Matsuo, Iwatsuka and Suzuoki 1973). However, in their adipose tissue, only 6-phosphogluconate dehydrogenase level was elevated, and acetyl-CoA carboxylase and malic enzyme levels were unchanged. Alloxan treatment resulted in decreases of lipogenic activity in adipose tissue and liver of yellow KK mice; 6-Phosphogluconate dehydrogenase and acetyl-CoA carboxylase activities were decreased in liver, but only 6-phosphogluconate dehydrogenase activity was reduced in adipose tissue. These findings indicate that the profile of insulin-inducible enzymes differs between liver and adipose tissue in the mice. Mechanisms, through which insulin stimulates lipogenesis of adipose tissue, appear not exactly the same between the rats and the mice. Furthermore, the predominance of liver over adipose tissue in lipogenesis is suggested to be one of the main factors responsible for the development of obesity in the mice.