Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98 +/- 0.37 to 2.47 +/- 0.71 ng per milliliter, mean +/- 1 S.D.) (P less than 0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6 +/- 27.8 to 40.6 +/- 15.8 ml per minute) (P less than 0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine-digoxin therapy may be partly due to digitalis intoxication.