The renal clearances of digoxin and creatinine were determined in seven premature neonates (mean gestational age = 29.9 wk, range = 26 to 36 wk) at a postnatal age of 1 to 9 days (mean = 4.1 days). The corrected renal digoxin clearance (mean, 10.4 ml/min/1.73 m2; range, 2.5 to 36.7) was highly dependent on gestational age and body weight, r being 0.95 and 0.96, respectively (exponential curve). The linear slope of corrected renal digoxin clearance vs. creatinine clearance plot approached unity (r = 0.99), indicating that digoxin and creatinine were handled similarly by the kidney in these premature neonates (i.e. glomerular filtration with some degree of tubular secretion). Our finding of slower renal digoxin clearance helps to explain the higher serum levels and longer half-life of this drug in premature neonates.