The pharmacokinetics of digoxin was studied in 14 healthy volunteers using concentrations measured radioimmunologically in the serum, saliva and urine. The subjects were given 0.75 mg of digoxin intravenously. Serum and saliva were obtained over a 72 hr period and urinary excretion rates over 6 or 7 days. Binding of digoxin to serum proteins was determined by ultracentrifugalization. A linear correlation between the serum and saliva concentrations was found. Salivary levels were equal to the unbound fraction in the serum. The half-lives of distribution did not differ between the serum and saliva. An erroneously short half-life of elimination was found in the serum, but in the saliva and urine it was found to be in the range previously reported. Salivary level measurements may be useful in pharmacokinetic studies and may have important clinical implications.