AbstractThe solubility behavior of O‐methyl cellulose (MC) in water was investigated in terms of the distribution of substituents along the cellulose chain as well as in the anhydroglucose (AHG) units. For this purpose, three different types of MC samples were prepared by respective homogeneous reaction, i.e.. (i) methylation of cellulose acetate (CA) prepared from cellulose triacetate (CTA), followed by deacetylation, (ii) methylation of CA prepared by direct acetylation of cellulose in a 10% LiCl–dimethylacetamide (DMAc) solution, followed by deacetylation, and (iii) methylation of cellulose with dimethyl sulfate in a 10% LiCl–DMAc solution. Their water solubility was compared with that of MC samples prepared by the alkali cellulose process, i.e., by the heterogeneous reaction, including commercial products. It was found that water‐soluble MC samples prepared by the alkali cellulose process exhibit a thermally‐reversible sol‐gel transition in aqueous solution, but all of the MC samples preapred homogeneous reactions show a normal phase separation in aqueous solution. This result gives a direct support for the consideration that the highly substituted glucose sequences present in the commercial MC act as “crosslinking loci” on warming. The distribution of substituents in the AHG units was estimated by 13C‐NMR method. The results on the water solubility of MC were also discussed in terms of the distribution of substituents in the AHG units.