Digitoxin is considered a risk factor for ventricular arrhythmias in hemodialysis patients. In a randomized, crossover controlled study, 55 hemodialysis outpatients with sinus rhythm were prospectively investigated in two 48-h periods of electrocardiographic monitoring, one on and one off digitoxin or vice versa. The frequency of ventricular ectopic beats (mean +/- SD) which were found in 31 of 55 patients (56%), was slightly higher on hemodialysis (10 +/- 28 beats/h) than in the following 20 h (5.4 +/- 10 beats/h) and the next day off hemodialysis (3.6 +/- 6.6 beats/h); however, no difference was seen in patients on digitoxin during hemodialysis (10 +/- 29 beats/h), in the following 20 h (4.8 +/- 15 beats/h) and on the next day off hemodialysis (1.2 +/- 6.6 beats/h). The frequency of ventricular bigemini, polymorphous ectopies, couplets, more than 30 ectopies/h, salvos and tachycardias (10 vs 9 patients) on and off digitoxin was about the same (n.s., Fisher test). Supraventricular bigemini, salvos, tachycardias, and atrial fibrillation, however, occurred in significantly fewer patients on digitoxin (3 vs 13) than in those off digitoxin (P = 0.01, Fisher test). It is concluded that digitoxin does not increase the risk of ventricular arrhythmias in hemodialysis patients. Digitoxin, however, may have a beneficial effect on the supraventricular arrhythmias frequently observed in these patients.