There have been few investigations into the role of ion channels in mammalian early embryonic development, despite studies showing that changes in ion channel activity accompany the early embryonic development of non-mammalian species and the proliferation of mammalian cells. Here we report that a large-conductance, voltage-activated K+ channel is active in unfertilized mouse oocytes but is rarely observed in later embryos. The channel activity is linked to the cell cycle, being active throughout M and G1 phases, and switching off during the G1-to-S transition. These changes in channel activity are accompanied by corresponding shifts in membrane potential. Inactivation of the channel during S/G2 can be prevented by exposing the oocytes to dibutyryl cyclic AMP or forskolin, an activator of adenylyl cyclase. Inhibition of protein synthesis with puromycin did not prevent inactivation of the channel at the end of G1 or its subsequent reactivation at the end of G2, indicating that the channel activity is not regulated by mitosis-promoting factor or cyclins.