The eCube is a sophisticated, highly integrated data acquisition system for recording electrical activity from up to 6,400 electrodes. The system acquires, processes, and analyzes action potentials, field potentials, and other physiological signals. Our eCube digital headstages are the smallest and lightest headstages on the market, enabling large-scale electrophysiology in small, freely behaving animals. Headstages are compatible with individual wire electrodes, microelectrode and microwire arrays, planar silicon probes, ECoG arrays, and epidural or scalp EEG electrodes. Programmable I/O facilitates interfacing to 3rd-party equipment for synchronous acquisition of behavior, stimulus, or video data. Our unique eCube server architecture allows a single eCube to support up to ten independent experimental rigs simultaneously.