Abstract New developments are described in the area of capillary electrophoresis combined with electrospray ionization-mass spectrometry (CE—ESI-MSD), a promising new method for the separation and mass spectrometric characterization of labile, polar or ionic constituents of biological mixtures. the varous experimental modes of capillary electrophoresis are reviewed. The ESI-MS technique is described and the significance of its combination with capillary electrophoresis is illustrated by MS analysis of large biomelecules. The design and performance optimization of a new ESI interface are discussed, including the influence of electrophoretic and MS operating parameters. Various examples from our laboratory illustrating the range of present application of this interface and direction of future development are presented. These include negative iion electrospray mass spectra of nucleotide co-enzymes, nucleotide mono-, di- and triphosphates and positive ion spectra of biologically important oligopeptides and proteins of Mr > 75 kilodaltons.