A rapid method for the determination of the substituent distribution in carboxymethylcellulose has been developed, involving hydrolysis of carboxymethylcellulose in 1.2 M perchloric acid and analysis of the mixture of carboxymethylated glucose residues and glucose by high-pH anion-exchange chromatography with pulsed amperometric detection. The peaks in the chromatogram were identified by combined gas-liquid chromatography-mass spectrometry after pertrimethylsilylation. Molar response factors for each of the constituent monomers were established by H-1 NMR spectroscopy. The degrees of substitution for three carboxymethylcellulose preparations determined by the proposed method and by a standard titration method were found to be in excellent agreement.