The hydrophobic interaction between long-chain alkyl groups of hydrophobically-modified hydroxypropyl methylcellulose (HM-HPMC) and indomethacin (IM) was studied using a fluorescence probe method in which pyrene molecules are allowed to associate with long-chain alkyl groups.In an HM-HPMC solution, the hydrophobicity of the pyrene environment markedly increased as the concentration of HM-HPMC was increased, indicating an increase of hydrophobic interaction between the long-chain alkyl groups. When IM was added to this solution, the hydrophobicity of the pyrene environment decreased as the IM concentration increased. Thus, it was suggested that the hydrophobic interaction between long-chain alkyl groups and IM caused a weakening of the hydrophobic interaction between HM-HPMC molecules themselves. When isopropanol (IPA) was added to an HM-HPMC solution, IPA weakened the hydrophobic interaction through long-chain alkyl groups. Thus, IPA caused an expansion of the intermolecular hydrophobic regions. For this reason, the amount of IM entrapped in these regions increased when the IPA concentration was increased. However, when the IPA concentration was further increased, the hydrophobic interaction finally disappeared. Thus, as IM molecules could no longer be trapped in the hydrophobic regions, the activity of HM-HPMC suppressing the growth of IM crystals disappeared.