Digoxin therapy was evaluated retrospectively in a group of 30, and prospectively in a group of 16 low-birth-weight, premature infants with cardiorespiratory symptoms due to persistent patency of the ductus arteriosus. The response to decongestive therapy was equivocal. Digoxin levels in serum varied between 1.5 and 13 ng/ml. Digoxin half-life in serum exceeded three days in four patients. Fourteen of the combined group of 46 infants had signs of toxicity of digoxin. High dosage, inadvertent overadministration, and variable clearance of digoxin, as well as special characteristics of the patients studied, are postulated as explanations for the high incidence of toxicity. This study suggests that digoxin therapy in low-birth-weight, premature infants with patent ductus arteriosus is not without risk.