A pneumatically assisted electrospray liquid chromatography/mass spectrometry interface has been modified for use with open-tubular supercritical fluid chromatography (SFC). The modified interface houses the SFC flow restrictor within the spray device. A sheath-flow liquid of methanol or methanol/water containing ammonium acetate flows coaxially to the restrictor. The addition of the sheath-flow liquid results in the ionization of analytes known to be in a neutral charge state during the chromatographic separation. The sheath-flow liquid also allows for the independent operation of the chromatograph and the mass spectrometer. Both could be operated under optimum conditions. The operation of the interface was optimized using a solution of poly(dimethylsiloxane) in CO2 introduced by continuous infusion. We also report the application of the modified instrument to samples containing amines and propoxylated alcohols.