The acidic microclimate pH (mupH) in poly(lactide-co-glycolide) (PLGA) devices has been identified as a major source of instability of encapsulated proteins and acid labile small molecules. A fast and reliable potentiometric technique for mupH measurement in thin PLGA films was developed and validated. Standard glass pH electrodes were coated with PLGA films, and the zero-current potential was measured with respect to a calomel reference electrode. The measurement was independent of external media pH but responsive to addition to the polymer films buffering salts from lyophilized solutions of various pH values. The contribution of additional diffusion and interfacial potentials in the electrochemical cell due to the presence polymer coating was determined to be roughly less than or equal to0.2 pH units by two independent measurements and slightly pH dependent. A highly acidic mupH (mupH < 3) developed in PLGA 50/50 films (similar to30-100 mum thick) after I day of incubation in a physiological buffer at 37 degreesC and remained acidic for 4 weeks. The ypH varied significantly with the thickness of the coating during extended incubation. The mupH of a 7 Pin thick coating rose to a neutral value (pH 6.5) after 1 week of incubation, but it remained acidic (pH 2-3.5) for 250 and 30 mum thick coatings. Hence, the microclimate pH measurement described here may be useful for mechanistic evaluation and mupH control of biodegradable polymer systems encapsulating labile molecules.