Atrial natriuretic factor (ANF) is a peptide produced by the atrium in response to increases in atrial pressure. It is a potent vasodilator and recent studies suggest that ANF may modulate vasomotor changes in patients (pts) with pacemaker (PM) syndrome. To evaluate the incidence of pacing mode on peptide secretion, plasma concentrations of ANF were determined in 32 pts (18 men and 14 women, mean age 71 +/- 4 years) with a DDD PM implant. Blood samples were collected one hour after a randomly assigned PM programming either in VVI or DDD mode at 70 ppm. Mean plasma ANF levels were 84.12 +/- 51 pg/ml in DDD mode and 156.0 +/- 15 pg/ml in VVI mode (p < 0.05). In 12 pts presenting ventriculoatrial retroconduction, the ANF levels were 77.16 +/- 50 pg/ml during DDD stimulation and 219.0 +/- 16 pg/ml during VVI stimulation (p < 0.05). ANF level was 88.50 +/- 46 pg/ml in DDD mode and 114.25 +/- 65 pg/ml in VVI mode in the 20 pts without AV retroconduction (p < 0.05). During DDD mode, 18 patients showed a DVI stimulation whereas 14 showed a VDD stimulation: the mean ANF level was 67.40 +/- 15 pg/ml during DVI and 100.40 +/- 28 pg/ml during VDD stimulation; the difference between these data was not significant. The increase in ANF levels during VVI pacing confirms the lower haemodynamic performance of this stimulation mode. The increase of ANF levels during VVI stimulation, which was in the subgroup without AV retroconduction, confirms the benefits of DDD stimulation also in this group of patients as well. Atrial pacing at physiological rates does not trigger the release of ANF.