The investigation was designed to test whether nicardipine and tiapamil interact with digoxin, resulting in increased plasma digoxin levels. Ten patients mean age, 67 years) taking 0.13 mg to 0.25 mg of digoxin daily were given nicardipine (20 mg TID), and eight patients (mean age, 77 years) taking 0.13 mg to 0.25 of digoxin daily were given tiapamil (200 mg TID). Plasma levels of digoxin and nicardipine, heart rate, blood pressure, weight, serum electrolytes, and serum enzymes were measured and the electrocardiogram was monitored twice before, four times during, and once after the intervention with a calcium antagonist. No measurements of plasma levels of tiapamil were made. A chest roentgenogram was taken before, during, and after use of nicardipine or tiapamil. Mean plasma digoxin levels increased significantly in patients receiving tiapamil (P less than 0.01), but the values returned to normal after treatment with the experimental drug was discontinued. A wide variation of plasma nicardipine levels was observed, but there was no proportionate correlation between these levels and changes in digoxin levels. Blood pressure decreased significantly (P less than 0.01) and heart rate increased significantly (P less than 0.05) in patients receiving nicardipine. Similar changes in blood pressure and heart rate were not seen in patients receiving tiapamil. Although the use of each calcium antagonist led to an increase in plasma digoxin levels, the effect of tiapamil was greater than that of nicardipine.