This paper discusses the miscibility of cellulose/poly(ethylene oxide) (PEO) blend systems from the view point of the relationship between hydrogen bond formation and regiochemistry of hydroxyl groups in cellulose. Thermodynamic examination of the systems using 2,3-di-O- and 6-O-methylcelluloses (23MC and 6MC) as cellulose model compounds was carried out by differential scanning calorimetry. The values of two parameters, interaction energy density characteristic, B, and interaction parameter, chi(12), assessed by the thermodynamic analyses indicated evidence of polymer-polymer interaction in 23MC/PEO blends and lack of interaction between 6MC and PEO in their blends. Optical microscopic observation of the blend systems revealed the same phenomena. Results of the two investigations support our proposal of a regiochemical effect of hydroxyl groups in cellulose analysed by Fourier transform i.r. spectroscopy; that is, primary hydroxyl groups at the C6 position of the glucose unit of cellulose interact predominantly with ether oxygen in PEG, while secondary hydroxyls at the C2 and C3 positions are not engaged in hydrogen bonding. However, in pure cellulose/PEO blend each negative magnitude of the values was much larger than the sum of the values of each parameter for the 23MC/PEO and 6MC/PEO blends, indicating the presence of secondary polymer-polymer interaction.