Hydrogen peroxide (H(2)O(2)) causes oxidative stress and is considered a mediator of cell death in various organisms. Our previous studies showed that prolonged (>6 h) treatment of Aplysia sensory neurons with 1 mM H(2)O(2) produced hyperpolarization of the resting membrane potential, followed by apoptotic morphological changes. In this study, we examined the effect of H(2)O(2) on the membrane conductance of Aplysia sensory neurons. Hyperpolarization was induced by 10 mM H(2)O(2) within 1 h, and this was attributed to increased membrane conductance. In addition, treatment with 10 mM H(2)O(2) for 3 min produced immediate depolarization, which was due to decreased membrane conductance. The H(2)O(2)-induced hyperpolarization and depolarization were completely blocked by dithiothreitol, a disulfide-reducing agent. The later increase of membrane conductance induced by H(2)O(2) was completely blocked by 100 mM TEA, a K(+) channel blocker, suggesting that H(2)O(2)-induced hyperpolarization is due to the activation of K(+) conductance. However, the inhibition of K(+) efflux by TEA did not protect against H(2)O(2)-induced cell death in cultured Aplysia sensory neurons, which indicates that the signal pathway leading to H(2)O(2)-induced cell death is more complicated than expected.