We propose a method to integrate an electrospray (ES) device to an atmospheric pressure photoionization (P I) source. We will employ a proprietary method to generate charged droplets that will undergo charge-repulsion to form volatilized analyte without producing ES positive ions. The positive ion spectrum will be due to PI only. By this means, the benefits of PI can be extended to non-volatile and thermally- labile compounds. PI has proven to be a general purpose ionization source for analyzing a wide variety of compounds, in many cases compounds not detectable by ES ionization (ESI) or atmospheric pressure chemical ionization (A PCI). PI is particularly well suited for drug-like compounds, and is much less susceptible to competition-for- charge and ion-suppression that affects ESI and APCI mass spectra. This proposal is a resubmission that contains new results that greatly raise the probability of success. We are confident that if provided SBIR seed money to test the feasibility in Phase I and solve the R&D issues in Phase II, that the ES/PI source would be immediately commercializable. The ES/PI source could also operate as an ES ionization source thereby providing dual ESI and PI capabilities for large molecules. The latter strategy would lead to rapid acceptance and widespread use in the pharmaceutical industry. PROPOSED COMMERCIAL APPLICATION: The pharmaceutical industry places increasingly greater demands on molecular analysis technology in terms of speed, quantitation, and generality. Development of a dual ESI/PI source would greatly expand capabilities and would be widely accepted into use as an enhanced ESI source.