We have measured the biliary excretion of 3H-digoxin in normal subjects by intestinal perfusion methods which impose minimal interruption of the enterohepatic circulation. In contrast to data obtained in patients with liver disease and postoperative patients with biliary fistulas, our data show that about 30% of an intravenous dose of 3H-digoxin reaches the digestive tract in 24 hr. Most of the excreted radioactivity is chloroform-soluble and presumably reabsorbably and most of this fraction is probably biologically active drug. The results suggest that (1) consideration of hepatobiliary function may be relevant in observations regarding digoxin pharmacokinetics and that this route may be exploited in trials of therapy designed to shorten the duration of digoxin intoxication.