The goal of this research is to develop and adapt the Vestec "Universal Interface" to couple conventional HPLC to electrospray mass spectrometry. The new Vestec interface, which has been successfully applied to coupling reversed phase HPLC at flow rates as high as 1.5 mL/min of aqueous effluent to electron impact mass spectrometry, produces an aerosol of droplets containing the sample and allows removal of as much solvent as desired without losing the sample or destroying the chromatographic fidelity. Electrospray mass spectrometry is an exciting new technique whereby molecular weight information can be obtained on proteins and other biopolymers with no apparent limit on size. We propose to develop a technique for charging the droplets emerging from the Universal Interface and transmitting the resulting charged droplets and/or multiply charged molecular ions to a quadrupole mass spectrometer. In this way spectra on proteins and other large biomolecules will be obtained similar to those already demonstrated for electrospray, but without the restrictions on liquid flow and composition inherent in the conventional electrospray technique. The ultimate goal is an instrument routinely useful in the biomedical laboratory for determining the molecular weights on subpicomolar components of complex biological extracts on-line with HPLC separation.