Nine horses with (naturally acquired) congestive heart failure were treated with 2.2 micrograms of digoxin/kg of body weight by the IV route, followed by 11 micrograms/kg administered orally every 12 hours thereafter. Furosemide was administered IV concurrently with IV administered digoxin every 12 hours. Serum concentration of digoxin was measured after the first (IV) and seventh (orally administered) dose. After IV administration, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase (t1/2 alpha = 0.17 hour), followed by a slower elimination phase (beta = 0.096 +/- 0.055 h-1, t1/2 beta = 7.2 hours, where beta is the exponential term from the elimination phase of the concentration vs time curve). Bioavailability after oral administration was 21.2 +/- 10.8%. After the seventh orally administered dose, serum concentration of digoxin peaked 1 to 2 hours later, and was 1.9 +/- 0.7 ng/ml (mean +/- SD). In 4 horses, a second increase in serum digoxin concentration was observed 4 to 8 hours after the initial peak, which possibly was evidence of enterohepatic recycling of the drug. Response to treatment included reduction in heart rate, peripheral edema, and pulmonary edema, but these could not be attributed to the digoxin alone because the horses were treated concurrently with furosemide.