The renal clearance of digoxin and creatinine were measured in eleven infants, aged one to five months, with congenital heart disease and heart failure. The renal clearances of digoxin were low at one month of age (50 ml/min/1.73 m2) but increased progressively until the adult range was attained at about five months of age (130-150 ml/min/1.73 m2). At any given age, however, the renal clearance of digoxin was almost twice as great as the simultaneously determined creatinine clearance (mean ratio 1.73). This stands in marked contract to older subjects where creatinine and digoxin clearances are usually similar. These data explain (in part) the larger digoxin dosage requirement of infants.