A pacemaker that adapts heart rate in response to the patient's metabolic requirements has been developed. The pacemaker uses breathing frequency and tidal volume as the indicators of physiologic demand. Maximal physical work capacity, anaerobic threshold, oxygen uptake (16 patients) and hemodynamic variables (9 patients) were assessed with fixed rate (VVI), atrial synchronous (VDT/I) and respiration-dependent ventricular (VVI-RD) pacing. All subjects attained their anaerobic threshold in stress tests with VVI pacing. The maximal physical capacity (p less than 0.001), work time to attain the anaerobic threshold (p less than 0.01) and oxygen uptake (p less than 0.001) were significantly greater with VVI-RD than with VVI pacing. The transition from the supine to the standing position was characterized by a significant increase of cardiac index at rest with both VDT/I and VVI-RD pacing as compared with VVI pacing. Progressive increments in the cardiac index and average left ventricular stroke work index were significantly different at submaximal and maximal exercise when VVI and VVI-RD were compared. At maximal exercise, mean cardiac output was also significantly different: 10.21 +/- 2.5 (SD) liters/min with VVI, 11.2 +/- 0.8 liters/min with VDT/I (p less than 0.05) and 12.65 +/- 3.1 liters/min with VVI-RD (p less than 0.05) pacing. Maximal oxygen extraction values were greater with VVI and VVI-RD pacing than with VDT/I pacing. Pulmonary artery end-diastolic pressures at maximal exercise were within the normal range with the three different modes of pacing. In conclusion, there is a significant (25%) improvement in exercise performance with VVI-RD pacing as compared with VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)