The relation of pacing rate to physiologic variables of metabolic demand was examined in 10 consecutive patients with a minute ventilation-sensing, rate-modulating ventricular pacemaker implanted for complete heart block. All patients had paroxysmal (seven patients) or chronic (three patients) atrial fibrillation and were referred for catheter ablation of the atrioventricular junction. Treadmill exercise testing with measurement of expired gas exchange and respiratory flow was performed before ablation and 4 weeks after pacemaker implantation, with the pacemaker programmed to both the fixed-rate VVI and rate-modulating minute ventilation VVIR pacing modes in random sequence. The relation of pacing rate to oxygen consumption (V̇O2), expired carbon dioxide concentration (V̇CO2), respiratory quotient, tidal volume, respiratory rate and minute ventilation was determined during exercise in the rate-modulating minute ventilation pacing mode. Pacing rate was highly correlated with minute ventilation (r = 0.89), respiratory quotient (r = 0.89), V̇CO2 (r = 0.87), tidal volume (r = 0.87), V̇O2 (r = 0.84) and respiratory rate (r = 0.84). The mean exercise duration increased from 8.3 ± 2.8 min in the fixed rate pacing mode to 10.2 ± 3.4 min in the rate-modulating, minute ventilation mode (p = 0.0001). The maximal V̇O2 increased from 13.4 ± 3.4 to 16.3 ± 4.1 cc/kg per min (p = 0.0004). The maximal heart rate achieved in the minute ventilation pacing mode was 136 ± 9.7 beats/min, similar to that observed in the patient's intrinsic cardiac rhythm before ablation (134.9 ± 30.1 beats/min, p = NS). Isoproterenol infusion at rates of 1 and 2 μg/min produced no change in pacing rate, suggesting that the rate-modulating algorithm of the pacemaker was capable of discriminating changes in transthoracic impedance related to respiration from those related to right ventricular stroke volume. Thus, rate-modulating pacemakers that measure minute ventilation by transthoracic impedance provide increases in pacing rate during exercise that closely parallel physiologic variables of metabolic demand. © 1989.