Methylcellulose (MC), a hydrophobically modified cellulose derivative, in an aqueous solution undergoes sol-to-gel and gel-to-sol transitions on heating and cooling, respectively. Using differential scanning calorimetry, MC in light (H2O) and heavy (D2O) water solutions has been investigated to elucidate the solvent isotope effect on the transitions. As a result, their transition temperatures are higher in H2O by about 4 A degrees C than D2O. This phenomenon is rationalized in terms of the strength of the hydrophobic attractive interaction; the strength is enhanced by D2O. We discuss the reason for the enhancement and the difference in the isotope effect between MC and a poly(N-isopropylacrylamide) polymer which shows an opposite trend to MC.