In this paper we report that the amplitude of the T-current changes in a cell cycle-dependent manner in single- and two-cell embryos, being large in unfertilized oocytes and decreasing after fertilization throughout the first cell cycle to a minimum in early M phase, before increasing again during late telophase. This increase can be prevented by arresting the cell cycle in metaphase, but is not prevented by cytochalasin D. During the second cell cycle the T-current remains large until late G2 phase when it decreases. Protein synthesis inhibition has no effect on the changes in T-current amplitude during the cell cycle. This finding, along with the observation that the size of the T-current does not increase until mitosis exit, suggests that cell cycle regulation of the current does not involve the cycling of cyclin-dependent kinase (cdk)1/cyclin B activity. Inhibition of the T-current with pimozide has no effect on cleavage. The cell cycle-dependent changes in T-current amplitude appear to be driven by the same cdk1/cyclin-B-independent clock that we have previously shown to drive cyclic changes in K+ channel activity in early mouse embryos. Thus, multiple ion transport systems in the preimplantation mouse embryo are controlled by this cdk1/cyclin-B-independent clock.