SUMMARY1. Tritiated digoxin was injected intravenously into euthyroid, hyperthyroid and hypothyroid rats. The rats were killed at intervals up to 24 h and tritium in serum and tissues counted.2. Serum concentrations of tritium in the hyperthyroid animals were less than in the control group, whereas the concentrations in the hypothyroid group were similar to those in the control group.3. Cardiac tissue concentrations of tritium were higher in the hyperthyroid group than in the control group, but in the hypothyroid group were similar to the control group.4. The decreased serum levels in the hyperthyroid rats were probably due to an increased volume of distribution.5. Pharmacological resistance to digoxin in hyperthyroidism must be due to some alteration in cardiac function and it is suggested that this is an increase in Na/K ATPase receptors.