This chapter describes the effects of dietary fructose on hepatic lipogenesis, blood triglycerides, and blood cholesterol in both experimental animals and humans with special emphasis on interaction with other environmental factors and genetic predisposition. In humans the liver appears to be a primary site of the synthesis of lipid from carbohydrate. Studies using the rat have shown that fructose is more readily converted by the liver into lipogenic substrates than is glucose. Studies in which various metabolic intermediates of lipogenesis were incorporated into fatty acids in experimental animals adapted to the feeding of fructose as compared to glucose have not produced clear-cut results. The lipogenic enzymes increased by fructose feeding, such as fatty acid synthetase, pyruvate kinase, pyruvate dehydrogenase, citrate lyase, and acetyl-CoA carboxylase encompass the key metabolic steps necessary for the conversion of carbohydrate to lipid by mammalian liver.