An electrospray ionization source has been coupled to a reflection time-of-flight mass spectrometer. By orienting the ion source perpendicular to the field-free drift region, the longitudinal energy spread of the ion packet has been substantially reduced, allowing a mass resolving power of over 1000 to be achieved for both low-mass and high-mass ions of biological interest. In addition, instrument sensitivity allows the routine detection of low-picomole and subpicomole quantities of large multiply charged species such as cytochrome c (MW = 12,360.9). The potential utility of this instrument for conducting rapid screening of chromatographic effluents is discussed in light of its simplicity, rapid scanning speed, and high sensitivity.