The effect of repeated oral doses of activated charcoal on intravenous digoxin kinetics was evaluated in a randomized, crossover study. Ten healthy subjects received infusions of 10 micrograms/kg digoxin alone and with 225 gm activated charcoal over 40 hours. Multiple serum digoxin concentration determinations were made after each dose by radioimmunoassay. Noncompartmental kinetic analysis was used. Digoxin clearance increased an average of 47% (range -2% to 119%) during charcoal treatment, from 12.2 +/- 2.0 to 18.0 +/- 2.9 L/hr. The volume of distribution at steady state decreased from 495 +/- 196 to 375 +/- 162 L, and the terminal t1/2 was shortened from 36.5 +/- 11.8 to 21.5 +/- 6.5 hr during charcoal treatment. Likewise, mean residence time decreased, from 41.1 +/- 20 to 19.9 +/- 7.8 hr. Kinetic predictions would suggest greater proportional increases in digoxin clearance in patients with renal impairment. We conclude that repeated doses of charcoal enhance the clearance of digoxin and should be considered for use in digoxin toxicity.