To define the relationship between digoxin dose and plasma concentration and the changes in body growth, 1181 plasma digoxin levels were measured in 644 infants and children receiving maintenance digoxin therapy. The drug was given intravenously to 166 patients and orally to 478. A significant linear correlation between dose and plasma concentration was observed (r 0.346 to 0.767 in the intravenous and 0.264 to 0.664 in the oral groups). Dosage differences explained 7% to 60% of the variability in digoxin plasma concentrations in various age and weight groups. The linear regression slope was greater in younger age groups, especially preterm infants weighing less than 1500 gm, and tended to decrease with age. The data (1) allow an approximate prediction of plasma concentrations of digoxin and their variability associated with changes in dosages in various pediatric age and weight groups, (2) permit an estimate of other pharmacokinetic determinants of digoxin plasma concentration and their changes with age, and (3) suggest that larger changes in digoxin doses in older children are necessary to achieve the same change in serum concentration that is achieved with smaller dose changes in the young infant. As a result, premature infants are more sensitive to and require smaller digoxin doses.