The effect of thyroid hormone and retinoic acid on the expression of CCAAT/enhancer binding proteins (C/EBPs) alpha and beta was investigated in rat liver during development. Congenital hypothyroidism caused a significant decrease in both C/EBP alpha and C/EBP beta gene expression at early stages of postnatal development. This effect was tissue specific since thyroid hormone had no effect on the level of C/EBP mRNAs in brown fat. Injection of 15-, and 30-day-old hypothyroid animals with thyroid hormone resulted in a slow recovery of the hepatic levels of both C/EBP alpha and beta mRNA levels. Retinoic acid was a very rapid and potent stimulator compared to thyroid hormone in hypothyroid animals. C/EBP alpha and beta protein levels were markedly diminished in hypothyroid neonates and the kinetics of induction of these proteins by thyroid hormone was faster than the one observed for the corresponding transcripts. The discrepancies observed between mRNA and protein levels suggest a translational or post-translational regulation of these genes as the major point of thyroid hormone action on these genes.