The pharmacokinetics of IV administered digoxin and the bioavailability of intragastrically administered powdered digoxin tables suspended in water were investigated in 6 clinically normal adult horses by 125I radioimmunoassay. The effect of 3 to 5 sequential IV doses of 5 micrograms of digoxin/kg of body weight at 2-hour intervals on a left ventricular index of contractility (Vmax) was assessed in 5 clinically normal horses. Standard pharmacokinetic equations and mean pharmacokinetic variables were used to derive parenteral and oral (loading and maintenance) doses for digoxin in horses. The calculated dosage regimens were administered and resulting plasma digoxin concentrations were monitored in 5 horses and 1 pony. Digoxin disposition after IV injection was triexponential. A rapid distributive phase with a half life (t 1/2 of 15 minutes was followed by a slow distributive phase with a t 1/2 of 4.1 hours. The biological disposition t 1/2 was 23.1 hours. The volume of distribution by extrapolation was 6.79 L/kg of body weight and 4.89 L/kg by the area method. The average bioavailability estimate for intragastrically administered digoxin was 19.2%. The Vmax increased significantly (P < 0.01) after IV digoxin administration. Greatest changes in Vmax were recorded after the first 2 injections (5 micrograms of digoxin/kg) corresponding to plasma digoxin concentrations of 0.83 and 1.68 ng/ml. Doses of digoxin were calculated as follows: IV loading 14, IV maintenance 7, oral loading 70, and oral maintenance 35 micrograms/kg/24 hours. When these doses were given to a group of horses, plasma digoxin concentrations measured 12 and 24 hours after administrated were mostly in the proposed therapeutic, nontoxic range of 0.5 to 2.0 ng/ml.