The effects of hydrogen peroxide (H(2)O(2)) exposure on Xenopus oocytes were examined. An application of 1 microL of 10% H(2)O(2) to oocytes voltage-clamped in 1mL of Modified Barth Saline (MBS: final concentration of 0.01% H(2)O(2)) induced a transient ionic current. This H(2)O(2)-induced current, however, was not transient but long-lasting in a Ca(2+)-free medium. The H(2)O(2)-induced current was independent of increases in intracellular calcium. Intriguingly, the H(2)O(2)-induced current was similar in signature to one stimulated by the removal of extracellular calcium (Ca(o)(2+)-inactivated current). Both currents (a) were inactivated by 1.5mM LaCl(3), GdCl(3), CdCl(2), NiCl(2), CaCl(2), or MgCl(2), but not by LiCl or KCl, (b) exhibited reversal potential shifts to more positive values with increasing external NaCl, (c) showed linear voltage-current (I-V) relationships, and (d) were reversibly inhibited by two chloride channel blockers, 200 microM 5-nitro-2-(3-phenylpropylamino)-benzoic acid and 250 microM niflumic acid. Additionally, H(2)O(2) was still able to induce current in oocytes loaded with either catalase or N-acetyl-L-cysteine, H(2)O(2) scavengers. These results imply that H(2)O(2) induces this ionic current possibly through the activation of Ca(o)(2+)-inactivated channels by an extracellular mechanism.