A fluorescent labeling procedure, which does not perturb macromolecular conformations, was employed to bind a rhodamine derivative to the reducing end of several water-soluble polysaccharides by reductive amination in the presence of sodium cyanoborohydride. Fluorescence correlation spectroscopy, atomic force microscopy, and size exclusion chromatography were used to demonstrate that the conformations of the polysaccharides schizophyllan, polygalacturonic acid (PGUA), succinoglycan, and several dextrans were maintained following the labeling procedure.