Steady state serum concentrations of digoxin were determined repeatedly in 34 infants with congenital heart disease. Simultaneous measurements of renal clearances of digoxin, creatinine and urea were obtained in 29 of the subjects. Serum digoxin concentrations were markedly higher in children under the age of 3 months than in those over this age, despite equal weight--adjusted 24 h doses. This finding was explained by a very rapid increase in renal digoxin clearance in the first 3 months--32 +/- 7 ml/min/1.73m2 at 1 week to 65.6 +/- 30 at 3 months. The subsequent increase in digoxin clearance was much slower, e. g. to 87.7 +/- 43 ml/min/1.73m2 at 12 months. Renal clearance of digoxin was equally well correlated with creatinine clearance (r = 0.87) as with urea clearance (r = 0.83), but it exceeded that of creatinine in all age groups. The findings indicate that both glomerular and tubular function is involved in the renal elimination of digoxin in young children, and that development of renal elimination of the drug parallels that of the maturation of renal function in the early months of life. The neonate and infant with congestive heart failure display impaired ability to eliminate digoxin. The impairment lessens rapidly with the development of renal function over the first 3 months of life. Diminished doses of digoxin should be advocated in this age group if therapeutic serum concentrations of the drug are to be maintained and toxicity avoided.