A system is described that uses laser desorption as a means of volatilizing small, thermally-labile biomolecules into the gas phase as neutral species. The desorbed molecules are then entrapped in a pulsed supersonic jet expansion of CO2and swept into a differentially pumped time-of-flight mass spectrometer. Laser induced R2PI at 280 nm or 266 nm through the π-π*transition is used to ionize these species softly at modest input energy.