Guidelines for Successful SFC/MS n the early days of on-line LC/MS, Arpino likened the union of these two instruments to the unlikely marriage of a bird and a fish: "Many believe this coupling is even more difficult to achieve than the love-match ... between two creatures that are at ease in their own environments but are not at home in both" (1). At first consideration, this combination of high-pressure and vacuum techniques does seem preposterous. Removing a molecule from its high-pressure solvent, transporting it preferentially over vaporized solvent to a partial vacuum, and imparting a charge on the analyte does seem a challenging feat. However, great progress was made and LC/MS applications have become routine.But what if the analyte were dissolved in a fluid that, at high pressure, solvated like a traditional liquid but transformed to an easily removed gas when the pressure dropped, leaving the analyte free to "fly like a bird"? This was the promise offered by supercritical fluid chromatography (SFC)/MS when research in the area began in the late 1960s (2-5). Admittedly, the analogy should not be carried too far. Nevertheless, the commonly used mobile phases in SFC/MS, such as C02, are much more easily pumped from a high to moderate vacuum system than are