The effect of left renal artery infusion of quinidine, 37.5 microgram (base)/kg/min on the renal clearance of ultrafilterable digoxin was studied in eight dogs given 0.06 mg/kg digoxin 24 hr previously. Digoxin was measured by 125I RIA, whose specificity was confirmed by HPLC. Within 15 min of the start of the infusion, the digoxin clearance decreased on the left 7.3 +/- 5.8 ml/min and on the right 6.1 +/- 6.4 ml/min, p < 0.02 and 0.05, respectively, compared to control. Quinidine infusion did not alter Cin. CDIG returned toward prequinidine infusion values after the infusion was stopped. We conclude that quinidine has a prompt and direct effect on the renal clearance of digoxin.