(1) Male, weanling rats were fed on diets containing 60% sucrose or 60% starch and the liver and adipose tissue were examined in vitro for their ability to oxidise glucose and to synthesise fat from glucose, using radioactive glucose as an indicator. (2) Compared with the livers of rats fed on starch those fed on sucrose showed a severe depression of both glucose oxidation and lipogenesis. When two forms of radioactive glucose were used, labelled in carbon-1 or universally labelled, the change in proportions of carbon dioxide liberated indicated that sucrose feeding had altered the metabolic pathways. (3) Adipose tissue also showed depressed lipogenesis after sucrose feeding and less carbon dioxide was formed from (1–14C) glucose but that from (U-14C) glucose was unchanged. (4) The effect of sucrose was apparent after 14 days feeding and persisted in experiments continued for 112 days. (5) The proportions of fat and glycogen in the liver and the fat content of the body were not altered by sucrose feeding. (6) Tissues from female rats behaved in the same way as those from male rats. (7) The effect of sucrose was compared in three strains of animals. The response of hepatic lipogenesis differed with the strain but lipogenesis in adipose tissue was depressed to a similar extent in all three strains. Glucose oxidation in both tissues varied in extent with strain; the strain that was not affected with respect to glucose oxidation in the liver was the most sensitive with respect to glucose oxidation in adipose tissue. (8) The sucrose effect was equally marked in fed and 24 h-fasted rats. (9) Sucrose included in a fat-free diet had a depressant effect on glucose oxidation and lipogenesis in liver but not on glucose oxidation in adipose tissue. (10) The lipids formed from radioactive glucose by adipose tissue were separated by thin layer chromatography and examined for radioactivity. The results indicated that the depression of lipogenesis largely or wholly affected the triglycerides. (11) Rats were injected intraperitoneally with radioactive glucose after feeding on the respective diets. The extracted fat from kidney and adipose tissue, but not that from liver and blood, showed a lower radioactive count after sucrose feeding. (12). It is suggested that sucrose might exert its depressant effect on metabolism by (a) reducing the amount of glucose-6-phosphate available through stimulating the formation of glucose-6-phosphatase and (b) altering the proportion of glucose metabolised via the pentose shunt by stimulating the formation of glucose-6-phosphate dehydrogenas