The substituent patterns of some chemically modified celluloses were characterized as a function of their size distribution, using size-exclusion chromatography coupled to both nuclear magnetic resonance spectroscopy (NMR) and cloud-point measurements. Intact and enzymatically hydrolyzed methyl cellulose (MC) was fractionated according to size, and the level of substitution of the fractions was measured off-line using NMR. Clouding behavior was also measured as a function of size. Clear differences between hydrolyzed and nonhydrolyzed samples were observed using both techniques. For samples that had been selectively hydrolyzed using cellulose-degrading enzymes, NMR data showed a direct link between the degree of degradation and the level of substitution. Differences in the clouding behavior highlighted changes in substituent levels and substituent patterns across the size distribution. The techniques gave valuable and somewhat complementary information on the substituent distributions of the samples before and after enzymatic hydrolysis.