Aim: To study the effect of hydrogen peroxide (H2O2) on persistent sodium current (INa.P) in guinea pig ventricular myocytes.Methods: The whole-cell, cell-attached, and inside-out patch-clamp techniques were applied on isolated ventricular myocytes from guinea pig.Results: H2O2 (0.1 mmol/L, 0.5 mmol/L and 1.0mmol/L) increased the amplitude of whole-cell INa.P in a concentration-dependent mmol/L) increased persistent sodium channel activity in cell-attached and insideout patches.The mean open probability was increased from control values of 0.015±0.004 and 0.012±0.003 to 0.106±0.011 and 0.136±0.010, respectively (P＜0.01 vs control).They were then decreased to 0.039±0.024 and 0.027±0.006,respectively, after the addition of 1 mmol/L GSH (P＜0.01 vs H2O2).The time when open probability began to increase and reached a maximum was shorter in insideout patches than that in cell-attached patches (4.8± 1.0 min vs 11.5±3.9 min, P＜0.01;9.6±1.6 min vs 18.7±4.7 min, P＜0.01).Conclusion: H2O2 increased the INa.P of guinea pig ventricular myocytes in a concentration-dependent manner, possibly by directly oxidating the cell membrane.