This paper presents an active microchannel neural interface (MNI) using seven stacked application specific integrated circuits (ASICs). The approach provides a solution to the present problem of interconnect density in three-dimensional (3-D) MNIs. The 4 mm2 ASIC is implemented in 0.35 μm high-voltage CMOS technology. Each ASIC is the base for seven microchannels each with three electrodes in a pseudo-tripolar arrangement. Multiplexing allows stimulating or recording from any one of 49 channels, across seven ASICs. Connections to the ASICs are made with a five-line parallel bus. Current controlled biphasic stimulation from 5 to 500 μA has been demonstrated with switching between channels and ASICs. The high-voltage technology gives a compliance of 40 V for stimulation, appropriate for the high impedances within microchannels. High frequency biphasic stimulation, up to 40 kHz is achieved, suitable for reversible high frequency nerve blockades. Recording has been demonstrated with mV level signals; common-mode inputs are differentially distorted and limit the CMRR to 40 dB. The ASIC has been used in vitro in conjunction with an oversize (2 mm diameter) microchannel in phosphate buffered saline, demonstrating attenuation of interference from outside the microchannel and tripolar recording of signals from within the microchannel. By using five-lines for 49 active microchannels the device overcomes limitations when connecting many electrodes in a 3-D miniaturized nerve interface.