A chip-CE/ESI/MS interface based on a low-sheath-flow design has been developed. A flat low-sheath-flow interface was fabricated to facilitate the coupling with a CE microchip. The interface consists of a PMMA reservoir block, a PMMA platform and a replaceable ESI sprayer. A CE interface was constructed by using a wire-assisted epoxy-fixing method to connect a 1.5 cm connecting capillary to the end of chip-CE channel. The opposite end of the connecting capillary was tapered to approximately 40 mu m od to fit tightly inside the back end of a removable fused-silica capillary ESI sprayer, which was also tapered to give a 10 mu m orifice. With this 1.5 cm connecting capillary, the sheath liquid flowed coaxially around the connecting capillary to create a low dead volume liquid junction at the interface between the connecting capillary and the ESI emitter. An advantage of the current design over existing chip-based CE/MS interfaces is that ESI emitter can easily be replaced. The analytical utility of this microdevice was demonstrated by the analysis of two synthetic mixtures: a series histamine antagonists and a mixture of synthetic peptides.