Digoxin serum and urine levels were determined by radioimmunoassay in 6 subjects (4 patients with heart disease and 2 volunteers without heart disease) who had been maintained on oral digoxin (0.25 or 0.5 mg daily). Observations were made during a 3-day control period and then during 8 days of concomitant digoxin and oral furosemide (40 mg daily) therapy. Serum digoxin levels determined 10 and 24 hr after each dose of digoxin averaged 1.2+/-0.1 ng/ml (M+/-SE) during control and 1.3+/-0.1 during the last 3 days on digoxin and furosemide. The daily urinary excretion of digoxine averaged 51+/-6% of the oral dose during control and 52+/-6 during the entire period of furosemide administration. The renal clearance of digoxin and creatinine averaged 94+/-7 and 87+/-11 ml/min, respectively, during control; corresponding values were 88+/-8 and 85+/-9 for urine collections demonstrating a distinct diuretic effect of furosemide and 87+/-8 and 75+/-10 for urine collections not demonstrating such an effect during diuretic therapy. The results suggest that the diuretic effect of furosemide does not significantly affect the excretion of digoxin