The purpose of this article is to elucidate the effect of integral sorption of moisture on gas permeation in glassy hydrophilic polymers. The oxygen and the simultaneous moisture sorption into various hydroxypropyl methylcellulose (HPMC) films were measured under a wide range of relative humidities using sorption analyzer equipment. Correspondingly, the oxygen permeability at different ambient conditions was measured using an oxygen detector. The solubility of oxygen in the HPMC film was found to be affected by the amount of water and therefore by the water state. At low moisture content, the water molecules are present as bound water, which promotes the sorption of oxygen in the HPMC films. At moisture content higher than 5%, water clusters are rapidly formed, which increase the affinity of HPMC polymer towards water rather than towards oxygen molecules, resulting in a decrease of oxygen solubility in the polymer. This was found to be the governing factor for the reduction in the oxygen permeability in glassy HPMC films at high water activity. This proposes a specific interaction between moisture sorption and oxygen transport in coating films like HPMC, which is of important aspect in the coating design and formulation. (C) 2010 Wiley Periodicals, Inc. J Appl Polyrn Sci 116: 3310-3317, 2010