The interaction between thyroid hormone (T3) and nutritional signals has been of interest for nearly a century. Thus, enhanced glucose production, absorption and utilization are associated with hyperthyroidism, whereas diminished glucose utilization and lipogenesis characterize hypothyroidism. Recent studies have uncovered what appears to be yet another area of interaction at the molecular level. On the one hand, a marked overlap exists between the changes in rat hepatic mRNA activity profile induced by hyperthyroidism and high carbohydrate administration. On the other hand, the patterns produced by hypothyroidism, starvation and diabetes are characterized by oppositely directed shifts. These findings may be due, in part, to a synergistic relationship between carbohydrate feeding and T3 administration in the induction of many hepatic lipogenic enzymes and their respective mRNAs. Studies both in the intact rat as well as in isolated hepatocyte cultures indicate that this synergism arises from the ability of T3 to multiply an intracellular signal derived from the metabolism of glucose. The development of recombinant DNA techniques can now be applied to the study of the interaction of T3 with nutritional signals. Initial efforts have demonstrated a hepatic mRNA (mRNAS14) rapidly responsive to both T3 and carbohydrates. With this probe, studies are under way to define the precise molecular mechanisms by which T3 and carbohydrates interact to influence gene expression.