The effect of multiple oral doses of activated charcoal on digitalis glycoside kinetics was studied to determine whether an activated charcoal regimen might have utility in treating patients with digitalis toxicity. Normal subjects were given intravenous infusions of digoxin 0.75 mg/70 kg or digitoxin 1 mg/70 kg iv followed by either water alone or water with activated charcoal in divided doses in a randomized crossover design. A subject with chronic renal failure was also given digoxin 0.5 mg/70 kg iv followed by water alone or water with activated charcoal. In six normal subjects, treatment with activated charcoal did not increase digoxin clearance (Cl) significantly (16.79 +/- 1.70 vs. 22.68 +/- 3.51 L/h). However, digitoxin Cl did increase significantly, from 0.24 +/- 0.01 to 0.47 +/- 0.04 L/h. In the renal failure subject, digoxin Cl increased from 3.6 L/h to 10.1 L/h. We conclude that the activated charcoal regimen is probably useful in patients with digitoxin toxicity. Although similar benefit is limited in patients with normal renal function who develop digoxin toxicity, it is possible that activated charcoal will be useful in patients with prolonged digoxin elimination due to renal dysfunction.