A rapid and sensitive radioimmunoassay for digoxin is described, which is capable of detecting as little as 25 μμg of digoxin. This assay, requiring as little as 0.1 ml of serum or urine, allows measurements of blood or urine digoxin concentration to be made easily within one working day. Patients judged on clinical grounds to have digoxin toxicity had average plasma digoxin levels of 3 mμg/ml. Patients thought to be adequately digitalized had average plasma levels of 1.6 mμg/ml, and those considered to be inadequately digitalized had average levels of 0.5 mμg/ml. These differences are highly significant (p < 0.001). The usefulness of plasma digoxin measurement in the detection and management of digitalis toxicity is discussed, and a role of the immunoassay in studying the pharmacology of digoxin absorption and excretion is briefly indicated.