The origins for abrupt adhesion loss at a critical relative humidity (RH) for polymeric adhesives bonded to inorganic Surfaces have been explored using a model poly(methyl methacrylate) (PMMA) film on glass. The interfacial and bulk water concentrations within the polymer film as a function of D2O partial pressure were quantified using neutron reflectivity. Adhesion strength of these PMMA/SiO2 interfaces under the same conditions was quantified using a shaft loaded blister test. A drop in adhesion strength was observed at a critical RH, and at this same RH, a discontinuity in the bulk moisture concentration occurred. The moisture concentration near the interface was higher than that in the bulk PMMA, and at the critical RH, the breadth of the interfacial water concentration distribution as a function of distance from the SiO2/PMMA interface increased dramatically. We propose a mechanism for loss of adhesion at a critical RH based upon the interplay between bulk swelling induced stress and weakening of the interfacial bond by moisture accumulation at the PMMA/SiO2 interface.