The relative importance of myocardial mass and serum concentration as determinants of tissue concentration of digitalis glycosides is unknown. Left ventricular hypertrophy was induced in rabbits by a technique of banding the aorta to produce a significant systolic gradient. The weight of the hypertrophied left ventricle of 6 animals exceeded that of the 5 control animals by an average of 49.6 percent. Tritiated digoxin (125 μCi/mg) in a dose of 0.045 mg/kg was given intravenously to each animal. Serum samples were obtained at 15 minute intervals for 2 hours at which time the animals were sacrificed and all tissues and sera analyzed for digoxin content. There was no significant difference in serial serum concentrations between the control animals and those with cardiac hypertrophy for the duration of the experiment. Results of this experiment revealed a definite linear relation between increasing serum concentration and tissue concentration of 3H digoxin. Tissue serum ratios were relatively constant and averaged 2.3. Variation of myocardial mass, normal or hypertrophied, is not a significant factor in tissue concentration of digoxin. Serum concentration rather than myocardial mass is the determining factor in myocardial tissue concentration of tritiated digoxin; thus, the presence of cardiac hypertrophy does not undermine the usefulness of the serum level of digoxin in providing an estimate of myocardial digoxin tissue concentration.