The micro-electrospray ionization source has been optimized for the specific analysis of neuropeptides such as neurotensin and methionine enkephalin. The source has the option of integrating nanoliter flow-rate desalting and preconcentration techniques into the micro-electrospray spray needle, eliminating post-column dead volumes. For neurotensin, the most sensitive neuropeptide analyzed thus far in this work, the injection of 10 muL of a solution containing 320 zeptomoles /muL gave an [M + 3H]+3 ion at m/z 558.4 with S/N of > 8:1. The MS/MS analysis of this peptide for the fragment ion at m/z 578.9 gave a S/N > 20:1 for a solution containing 32 attomoles /muL.