We have examined the influence of hypothyroidism and thyroid hormone replacement on hepatic levels of Spot 14 and thyroxine binding prealbumin mRNAs determined by dot hybridization and by Northern blot hybridization to specific complementary DNA probes. A marked reduction in Spot 14 mRNA was demonstrated in hypothyroidism, compared with the euthyroid state. T3 replacement of hypothyroid rats, using a wide dose range of T3 (1–20 μg) and 6 and 72 h time points, demonstrated no sustained effect at 6 h, but a dose-dependent stimulation of Spot 14 mRNA at 72 h after daily treatment with T3 was commenced. In contrast, no effect of hypothyroidism or T3 replacement on hepatic levels of thyoxine binding prealbumin mRNA was demonstrated, indicating the specificity of thyroid hormone action. T3 treatment of euthyroid rats was also associated with a dose-related stimulation of Spot 14 mRNA levels. The effect of hypothyroidism and T3 treatment of the rat on hepatic Spot 14 mRNA contrasts with divergent regulatory influences of thyroid status in the anterior pituitary and ventricular myocardium demonstrated using identical animal models, indicating the tissue specific influences of thyroid status.