The interaction between copovidone and Carbopol 907 is pH dependent. When the pH of an aqueous solution fell below pH 4.5, a water-insoluble complex began to form and precipitate. This complex resulted from a hydrogen-bond-induced interaction between the carboxylic groups in Carbopol 907 and the carbonyl groups of N-vinylpyrrolidone repeat units in copovidone. Consisting of these two polymers at an approximate 1:1 weight ratio, the complex was an amorphous material with a glass transition temperature of 157 °C. The interpolymer complexation in situ was applied to modify drug release properties of Carbopol 907-based theophylline matrix tablets. The effect of copovidone on drug release was dependent on the pH of the dissolution medium. In a 0.1 N hydrochloride acid solution at pH 1.2 and 50 mM acetate buffer at pH 4.0, an insoluble tablet matrix was formed as a result of the in situ interpolymer complexation, and theophylline was released therefore via Fickian diffusion. In a 50 mM phosphate buffer at pH 6.8, drug release from the matrix tablets was still impacted by the in situ interpolymer complexation because of the low-pH microenvironment induced by Carbopol 907. As a result, drug release rate of the matrix tablet containing both polymers at pH 6.8 was slower than that of the matrix tablets containing individual polymers. We observed similar drug release rates at both pH 1.2 and pH 6.8 between tablets containing the physical blend of these two polymers and tablets containing preformed interpolymer complexes.