Beta blockers in patients with sick sinus syndrome (SSS) may prevent supraventricular arrhythmias, systemic hypertension and myocardial ischemia, but may cause excessive depression of sinus node function. In 8 patients with SSS and a permanent pacemaker, the effect of chronic oral pindolol on sinus rate and pacing frequency was compared with that of propranolol in a double-blind crossover trial. In all patients the pacemaker was programmed to a rate of < or = 50 beats/min. Holter monitors, obtained at baseline and on each drug, were used to calculate peak ambulatory sinus rate, number of paced beats per day, maximal number of paced beats per hour, and percentage of hours with paced beats. The peak sinus rate with pindolol therapy was 24% higher than with propranolol (p = 0.001). During pindolol therapy, the number of paced beats per day and maximal paced beats per hour were reduced 54% (p = 0.04) and 61% (p = 0.02), respectively, compared with propranolol. Patients with SSS who require beta-blocker therapy for tachycardia, systemic hypertension or angina pectoris may have less bradycardia when treated with pindolol rather than propranolol. Beta blockers like pindolol, which cause less sinus node depression, may obviate the need for prophylactic permanent pacemakers in patients with SSS, and may help to prevent chronotropic incompetence and pacemaker syndrome in patients already treated with a VVI device.