In situ fatty acid synthesis has been measured with ³H₂O in anaesthetised lean and obese Zucker (fa/fa) rats. The accumulation of fatty acids was increased in both the liver and adipose tissue of young fa/fa rats as a result of both an increased rate of lipogenesis and an increase in tissue mass. Whereas total hepatic lipogenesis increased with age, total adipose tissue lipogenesis decreased in older fa/fa rats. Experiments with hepatectomized rats showed that the liver was the major site of the excess fatty acid synthesis in fa/fa rats. The enhanced rate of lipogenesis in fa/fa rats was abolished by either pairfeeding or streptozotocin treatment. The results suggest that the increased fatty acid synthesis in fa/fa rats is secondary to the hyperphagia, hpyerinsulinaemia, and increased mass of hepatic and adipose tissues.