We have developed a method for the rapid analysis of oligosaccharides and their degradation products by chromatographic separation on Bio-Gel P-4 (-400 mesh). Flow rates of 64 ml cm-2/h-1 can be attained at 55-100 psi with either a single column of 0.6 × 100 cm or two coupled columns each 0.6 × 100 cm, permitting analyses to be carried out in 1.5 or 3.0 h, respectively. Differences of 1 glucose equivalent can be precisely distinguished for oligomers at least as large as 15 glucose equivalents. The applicability of this method for the analysis of glycoprotein-derived oligosaccharides is demonstrated. By assigning a value of 1 glucose equivalent per neutral sugar residue and 2 glucose equivalents per amino sugar residue in such oligosaccharides, the effect of various exo- and endoglycosidase digestions can be rapidly and precisely monitored. These columns are extremely stable, providing continuous operation for at least 9 months with over 300 sample applications without deterioration.