A B S T R A C T To assess the effect of starvation and to explore the potential interrelationship of starvation and thyroid status at the pretranslational level, we have analyzed by two-dimensional gel electrophoresis, the hepatic translational products of starved and fed euthyroid and hypothyroid rats. 5 d of starvation resulted in a statistically significant change in 27 of 240 products visualized, whereas hypothyroidism caused a change in 20, both in comparison with the fed euthyroid state. Of considerable interest was that 68% of all changing messenger (m)RNA sequences were common to the hypothyroid and starved groups and showed the same directional shift. Further, both starvation and hypothyroidism yielded comparable decreases in total hepatic cytoplasmic RNA content. Although it has been well established that the level of circulating triiodothyronine (T3) and the level of hepatic nuclear receptors fall in starvation, this reduction cannot account for the observed decrease of total hepatic RNA nor for all of the alterations in the concentrations of specific mRNA sequences. Thus, administration of T3 to starved animals in a dose designed to occupy all nuclear T3 receptors fails to prevent the fall in total RNA and the majority of starvation-induced changes in the level of mRNA sequences. Moreover,The results of this study were reported in part at the Na- (1)(2)(3)(4)(5)(6)(7)(8) and also a decrease in hepatic nuclear T3 receptors in the rat (8)(9)(10)(11)(12). Associated with the effect of starvation on T3 receptor capacity and content are alterations in the incremental response of two hepatic enzymes, malic enzyme (ME) and a-glycerol phosphate dehydrogenase (a-GPD) to a given dose of T3 (8). Starvation and hypothyroidism are known to impair protein synthesis (13)(14)(15) and to result in a decrease in hepatic protein and RNA content (16,17).