The motivation of this work was to study some of the properties of nanoelectrospray operation under conditions where the entire sprayed liquid is vaporized and inhaled into the vacuum system. Under these conditions the desolvation requirements, sampling efficiency, concentration versus mass sensitivity, and molar response characteristics of various compounds were studied. The combined efficiency of ion production from solution and transfer into the vacuum system, referred to as sampling efficiency, is presented under various inlet conditions including different flow rates, solution compositions, and compound types. Under ideal solvent conditions the results for favorable compounds show sampling efficiencies of 70–85% at flows in the range of 50–500 nL/min. Efficiencies were lower for aqueous samples and compounds of different structures gave different molar response factors under these high sampling efficiency conditions. The relative molar response factors are presented in terms of those observed with higher flow rate sources which operate at significantly lower sampling efficiencies. In all cases, operating in this flow regime, the ion count rate was directly proportional to the absolute mass of analyte molecules entering the source. The experimental source used to carry out these studies included gas nebulization to stabilize the electrospray process, a heated laminar flow chamber to enhance desolvation and ion production, and various atmosphere-to-vacuum aperture diameters to maximize ion transfer. Copyright © 2006 John Wiley & Sons, Ltd.