Abstract Interest in supercriticla-fluid chromatographyy (SFC) of biological samples has recently increased. The following is a summery of recent progress in SFC—mass spectrometry interfacing and its application to the analysis of high-molecular-weight biopolymers. The approaches taken in several intérface designs and results obtained with each are presented and compared. Areas which are of special concern in working with high mass, thermally labile, or polar analytes include interface heating and flow restrictor design. These topics are discussed in light of previous work, and directions for further study are suggested.