Abstract. Microcolumn liquid chromatography and capillary electrophoresis facilitate isolation of biological macromolecules at subnanogram levels. In order to characterize structurally such small amounts of labile materials, it is essential to develop new nanoscale sample treatment approaches and highly sensitive analytical techniques for the determination of biomolecular fragments. Progress in this area is summarized, using selected examples of the amino acid, peptide, and oligonucleotide separations.