To investigate the status of the sodium-potassium pump in cells of human subjects with abnormal thyroid function, we measured the number of pump units as well as the cation transport activity of the pump in erythrocytes from 23 hyperthyroid and 7 hypothyroid patients. It was found that the number of Na⁺-K⁺-ATPase units in erythrocytes (as measured by ouabain binding) was significantly reduced in hyperthyroidism (mean 36% below controls, p < 0.001). The rate of rubidium uptake by the same cells was also reduced, but to a smaller extent (mean 9%, p < 0.02). These changes were reversible with control of the hyperthyroidism. Hypothyroid individuals showed changes in erythrocyte Na⁺-K⁺ pump which were in the opposite direction to those seen in hyperthyroidism. It is concluded that thyroid hormone exerts a marked negative influence on the number of Na⁺-K⁺ pump units in one easily available human cell type. The direction of the effect suggests a complex relationship between thyroid hormone and the level of the Na,K-ATPase in any one tissue. Whatever the cellular mechanism responsible for the effects observed in the red cell, these changes should provide a measure of thyroid hormone action at a cellular level and this may prove useful in the study of thyroid hormone physiology in man.