A recent study has reported the presence of a circulating KCNH2 (hERG) current-activating factor in the serum of heart failure (HF) patients with ventricular tachycardia (VT) or fibrillation (VF) (Sugiyama et al., 2011). It was shown that the KCNH2 current-activator enhanced hERG channel macroscopic tail current following depolarising voltage clamp commands, and this was hypothesized to be pro-arrhythmic. The aim of this study was to use computer models to evaluate the functional effects of an augmented IKr tail current in ventricular cell and tissues models under normal and HF conditions. Two biophysically detailed computer models for human ventricular action potentials developed by ten Tusscher et al. ( 2006) (TNNP) and O’Hara et al. ( 2011) (ORD) were implemented in this study. Simulation of HF condition was based on extant experimental data of HF-induced membrane ionic channels including a reduction of the current densities of INa ,Ito1, IKs, IK1 and INaK by 57%, 36%, 61.7%, 56.3% and 42% respectively; an increase of INaL density by 43% and its inactivation time constant by 25%. As experimental data also suggested a 50% reduction in the SERCA protein level in HF, a 50% reduction in SERCA uptake activity was also assumed. In both normal and HF conditions, experimental data of the KCNH2 current-activator on hERG tail current (Sugiyama et al., 2011) was used to modify IKr incorporated into the two models, together with an assumed reduced (case-1), increased (case-2) or unchanged (case-3) IKr step current during voltage-clamp. Simulation data suggested that case-1 resulted in a negligible APD increase in the TNNP model (2.5%, 4.4% and 2.1% for endo-, mid- and epi-cells respectively), but a more remarkable APD increase in the ORD (33.1%, 28.8% and 37.5% for endo-, mid- and epi-cells respectively) in normal conditions. In HF condition, it resulted in a dramatic APD prolongation in the endo- and epi-cells, a non-repolarisation in the mid-cell model. The quantitative differences in APD prolongation in the two models may be attributable to their different ionic channel current densities. Case-2 resulted in a slight APD reduction in both models in the normal condition, but a more dramatic APD reduction in the HF condition. Case-3 resulted in a negligible APD reduction in both models in the control and HF conditions. In conclusion, the presence of circulating KCNH2 current-activating factor can either prolong or shorten ventricular APDs in the HF condition, depending more on the change to the IKr step current amplitude, than the increased IKr tail current. Therefore, the hypothesized pro-arrhythmic effect of the circulating IKr current-activating factor (Sugiyama et al., 2011) in serum from HF patients is likely to depend crucially on overall modulation of IKr and this warrants further experimental investigation.