Thyroid hormones (TH) elicit a wide variety of metabolic and physiological responses in several tissues of higher organisms. The majority of these effects require the interaction of TH with protein receptors located at the cell nucleus. However, exranuclear actions of TH have elicited growing interest during the last decade. Red blood cells have been shown to possess plasma membrane-binding sites for both T3 and T4. Using this as a cellular model, a direct stimulation of erythrocyte membrane Ca++-dependent ATPase (Ca++-ATPase) by physiological concentrations of TH has recently been demonstrated (1,2). Among TH analogues, T4 exerts the highest stimulatory effect on basal enzyme activity which is not dependent upon prior conversion to T3 (3). This effect of T4 requires the mediation of calmodulin (CaM), an ubiquitous cytosolic protein which plays a major role in the regulation of Ca++-ATPase (4).