Skeletal muscle is one of the major target organs for thyroid hormone. The muscles most commonly affected are those used during prolonged effort (slow-twitch muscles). One of the major clinical features is the shortening of the Achilles-tendon reflex time in hyperthyroidism and its prolongation in hypothyroidism. Most of the peripheral effects of the thyroid hormones can be ascribed to the action of triiodothyronine (T2), which is produced by de-iodination of thyroxine (T4) in liver and kidney. From the plasma, T3 is actively transported into skeletal muscle. The Ca2+ ATPase in skeletal muscle is responsible for removal of Ca2+ ions from the cytosol into the sarcoplasmic reticulum (SR) during relaxation, and the Na+, K+ ATPase in the plasma membrane is responsible for restoration of the membrane potential after excitation. The concentrations of Ca2+ ATPase and Na+, K+ ATPase in rat skeletal muscle have been shown to increase four- and 10-fold, respectively, in the transition from the hypothyroid to the hyperthyroid state. In humans, a linear correlation between the Na+, K+ ATPase concentration of skeletal muscle and the free T4 index was established. Significant effects of T3 on Ca2+ ATPase and Na+, K+ ATPase can be detected 24 h after a single injection. These effects are mediated by increased production of mRNA for the respective proteins, initiated by binding of T3 to nuclear receptors. Passive fluxes of Ca2+, Na+ and K+ also show a significant rise after T3 treatment. The increase in passive fluxes of Na+ and K+ can be detected before the rise in the concentration of Na+, K+ ATPase, suggesting that T3. In addition to its nuclear effects, may have a direct effect on the plasma membrane. Apart from their significance for muscle function in thyroid disease, the changes in Ca2+ ATPase and Na+, K+ ATPase will be important in other conditions where T3 and T4 levels show dramatic changes, i.e. during postnatal development, starvation and undernutrition, as well as in non-thyroidal illness (low-T3 syndrome).