To determine whether plasma ANP and/or BNP levels can be used to detect limitations in daily physical activity after pacemaker implantation, we measured plasma ANP and BNP levels at a pacemaker follow-up clinic in 56 patients (62+/-15 yrs, 2AAI, 9VVI, 34DDD, 7VDD and 4 rate-responsive modes), daily physical activity evaluated by a specific activity scale questionnaire (METs) and VO2 max obtained by expired gas analysis during ergometer exercise. A very close correlation (n=6, r=0.89, p<0.05) was obseved between. ANP in patients with daily physical activity class III (2-4 METs, n=21) was significantly higher than class II (5-6 METs, n=23, p<0.01) and class I (>7 METs, n=8, p<0.01), while BNP in class III patients was significantly higher than in class II (p<0.0001) and class I (p<0.0001) patients. Significant correlations between daily physical activity and BNP (r=-0.64, p<0.0001) and ANP (r=-0.43, p<0.001) were observed. Physiological pacing mode did not necessarily offer a better profile for BNP levels compared with non-physiological pacing modes. Patients with ventricular pacing (wide QRS: VDD, RR-VVI and VVI) showed significantly high ANP (p<0.01) and BNP (p<0.01) levels compared with those in patients with atrial pacing (narrow QRS: AAI and RR-AAI). During exercise, plasma catecholamines and ANP levels were significantly elevated, however, BNP levels, which were already elevated at rest, did not change significantly, and reflected a limitation of daily physical activity. The present study revealed that 37.5% of the patients displayed an elevation in BNP and this was judged to be a limitation of physical activity class III being equivalent to NYHA II or more. Elevated resting BNP levels reflected a limitation in daily physical activity in these patients. These findings suggested a third condition for physiological pacing--synchronization of ventricular contraction (narrow QRS pacing)--in addition to the two conventional conditions of atrioventricular synchrony and rate-responsiveness.