In the present study, we studied the ability of glutathione (GSH) to detoxify exogenously applied cumene hydroperoxide (CHP). Exposure of leech Retzius nerve cells to CHP (1.5 mM) induced a marked prolongation of the spontaneous spike potential of these cells. Early after depolarization, and a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated by a rapid repolarization were recorded. GSH (0.2 mM) significantly inhibited the effects of CHP on the duration of the action potential and suppressed CHP-induced spontaneous repetitive activity. Voltage-clamp recordings showed that CHP (1.5 mM) caused significant changes in the outward potassium currents. The fast and slow steady part of the potassium outward current was reduced by 46% and 39%, respectively. GSH applied in a concentration of 0.2 mM partially blocked the effect of CHP on the calcium-activated potassium currents. The fast and slow calcium-activated potassium currents were suppressed by about 20% and 15%, respectively. These results suggest that the neurotoxic effect of CHP on spontaneous spike electrogenesis and calcium-activated potassium currents of leech Retzius nerve cells was reduced in the presence of GSH.