Serial serum digoxin concentrations were measured over a 10-day period in 15 low birth weight infants requiring digoxin therapy. The calculated total body digoxin clearance (TBDC) was found to be highly dependent on gestational age and body weight, with dose-normalized, steady-state digoxin concentrations inversely related to the same factors. Because of the decreased TBDC in low birth weight infants, our data support the recent recommendations in the literaure to reduce maintenance doses of digoxin in these infants. Our study has further demonstrated that the reduction should be proportional to both gestational age and body weight.