The mechanism and significance of intracellular entry of thyroid hormones has been studied in cultured cell lines. These have included rat myoblasts, mouse and human neuroblastoma cells, human medulloblastoma cells, and human glioma cells. All cells tested possessed a saturable, energy dependent transport system for T3 located at the plasma membrane that is important for uptake of the hormone by the cell nucleus. In addition, rat myoblasts and mouse neuroblasts showed stereospecific uptake and the latter showed saturable uptake of T4 as well as T3. Differentiation of neuroblastoma cells, induced by butyrate, was shown to be accompanied by a transient increase and then a decrease in T3 transport. The myoblasts were also used for a study of mechanism of induction of creatine kinase during cell differentiation. This appeared to depend on one or more short lived proteins, encoded by short lived mRNA(s) that selectively regulate the stability of the inducible mRNA.