Objectives. The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors. Background. The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors). Methods. Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up-down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control). Results. In protocol 1, the mean ± SD DFTs were lower during the first three cycles than after 10 s of VF (3.0 ± 4.1 J for the first VF cycle vs 15.8 ± 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFT for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 ± 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 ± 2.2 J), whereas the DFT for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 ± 2.7 J for the first VF cycle) than that induced from the LV. Conclusions. This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.